so it's my opportunity to introduce you
all to a doctor excu from the University

of Georgia try not to hold that against
him and he is an associate professor in

the College of Engineering and the
director of the computational and you

know biomechanics laboratory there's a
lot of other things on here but I'm just

gonna go ahead and get started and let
dr. Wong kind of tell you about his talk

today he's gonna talk titled interfacial
mechanics of cell nano particle systems

a computational perspective thank you
thank you thank you Michael for your

introduction it's my great pleasure to
be here

to briefly discuss my research I have
done the past few years the first thing

I wanted to say is the main work is from
the computation of mahagony simulations

I'm a computational guy so I haven't
done any kind of experiment work so most

of my work is from the view of the
computational modeling simulation to

understand this problem and the
experimental validation from micro

operations so you can call me my name as
XQ my Chinese name actual name is Chen

chow
it's very difficult to pronounce for

most of my colleagues and my students so
I just let him to call me xq instead of

essential so I joined the UGA into
cilantro so at that time we form the

newest college of engineering in Georgia
in 2012 okay so before I talk about the

material let's try to acknowledge my
collaborator and my students ok so this

is my lab kind of picture and this is my
groups and County I have a full actually

for graduate students and two visiting
scholars and long for undergrads in my

lab and I graduate to PD in the last
five years post them get a faculty job

one is in China one is in the Saudi
Binghampton in from this year and my

major crabber it meaning from the UGA
and a fear from the outsider UGA the

major crabber is the one is from
computer science and a lot of truth from

physics and chemistry so I would like
ecology the their kind of contribution

and the corporations and also I would
like to acknowledge the funding support

from the NSF and edge so let me give you
a brief introduction my the overview my

lab okay what I'm doing okay so the
ultimate objective for my lab is to

understand the fundamental principles
that control mechanical property or

behaviors materials in both engineering
and biology by virtue of the theoretical

Isis computational modeling and
experiment that experimental

investigation so as I said I never done
any kind of experiments

kind of work so these parties for micro
operations so my current research frauds

have a three area one of the straws area
is mechanics by logic materials so I

mainly study the brain foldings okay I
studied the fundamental principle of the

brain folding from the mechanical
viewpoint okay and the thrust of number

two is mechanics nanomaterials so I have
done lots of two-dimensional materials

and the crystalline materials and
Calabro is one professor in physics for

this type of experiment validation and
the third area is serenella particle

interactions so this area I try to
understand the fundamental mechanism of

cell mallepalli interactions okay and
help we can on better understand the

interaction and for the drug delivery
design so that's the three area I have

kind of working on and today I'm meaning
talk about the cell metabolic system and

the major computational tools I have
used in the past few years

wellness molecular dynamics image
okay that including Auto Tomica

simulations and course screen molecular
my simulations and also I use a lot of

final analysis for these brain stuff so
that's the over you my Condor work in

UGA so today I'm going to focus on the
nano sail teleporting into actions so

let's take a look why we are interested
in this there another party into action

right yeah one other thing everyone know
that right not a particle right now

everywhere everywhere
we have nano particle in incarnate nano

particle in daily life so one of wallet
problem we have see a lot is air

pollution okay everyday right ninety
percent every day is spent in door like

sometimes our door okay and actually we
have a breeze a lot yeah and these kind

of air actually pearl polluted those
type of nano particles or micro

particles right and this particle will
from your long interacts with your long

and in your lung cells okay and a lot of
one I think right now is very hot area

for the dissolve of flexible electronics
for diagnosis or prognosis or even

treatment for many many different kind
diseases that this is one of the picture

show these dissolve electronics made of
a kind of slick home and polymer

material right to detect the brain
signals right that that's kind of thing

and also we have seen similar kind of
stuff using on the heart right covered

on the heart and try to understand your
heart behavior okay I'll put those

signals these things are actually
devolve particles now the particle

dissolve eventually dissolve into your
in your blog okay and I think this one

everyone don't use right especially
ladies actually I use every day for

these facial cleaners or or kind of face
cream all these same actually have lots

of nanoparticles and absorbed by your
skin

yeah and a lot of things about these
daily cookies okay anyway my song enjoy

a lot this this kind of stuff this type
of cookie especially the colorful very

colorful more colorful cookies they have
a lot of those titanium nanoparticle

inside okay and this titanium of course
eventually I just in your body right go

to your go to your body cells those
things right so all these things are

talking about nanoparticle interact with
your body cells

so for nanoparticle right we will see
both advantage and disadvantage so let

me give you a couple example for
disadvantage right was a frustration

with a nanoparticle so this is a one of
the imaging shows the cell try to up

take these big one dimension of fibers
okay you see this fiber actually

penetrates through yourself this cell
feel not very comfortable okay and he

tried to update these nano fibers or
fibers but the fiber actually cannot be

absorbed it right and these penetrates
through the cell the cell feel very

stressful and these type of thing
actually costs informations same thing

there's a lot of picture tells us about
these cell interaction with the

two-dimensional material this is
actually made of graphene okay so the

graphing actually also can penetrated
through your cell membrane right getting

inside the cell the cell has not also
feel very stressful and not very healthy

for the sales development yeah so these
are cases for frustration for

nanoparticles but we also see lots of
benefit from the nanoparticles right for

example the drug delivery okay that's a
very huge amount of the part of a

nanoparticle for for applications right
and another particle co-leader with

white blood cell right these are kind of
nanoparticle this is a white process

they're counting on that right that's
will be helped to deliver the drug right

to the target area and also avoid these
kind of degradation

similar thing we have this nanoparticle
Coral complex these are calling coating

with this narrow
particle on the surface is neither is a

kind of Carlo complex that also we
increase this particle circulation and

target to the certain area for for
diseases and the solar picture also say

show the similar stuff like a drug
delivery system right so these are

typical benefit we haven't seen for the
sale teleporting interactions

maintaining focus on the drug delivery
system and for nanoparticle right as we

know the another particle size is from
from 10 to the minus 9

ok nanometers to 10 to the minus 6
that's go to micro sized meter right and

there are lots of different type of
nanoparticles most of the here like a

biological nanoparticles and in terms of
nanoparticles shape right for

fabrication we haven't seen lots of
different kind of nanoparticle shape I

the most popular ones though of course
is a severe shape right and you have

this kind of star shape you have a wrong
shape and even you have this kind of

liquor soil right and the also loss of
those different kind another particle

shapes and actually the shape of
nanoparticle inference a lot whole

another particle object by the cells
yeah for the cell okay this is a picture

for sale right and they made the
majority work I have done here I'm not

going to study the the namib particle
interacts a cell with inside a cell how

those cell intact with this organs right
I'm going to study the nanoparticle

hollom at a party will penetrate a
sueded membrane right and mature the the

one of the major barrier or major
prevent preventive for the cell attack

with the nanoparticle is the cell
membrane so I'm going to study the cell

membrane how the cell membrane interacts
with another particles one of the big

issue right we have see for drug
delivery right through these nano

carrier right and deliver the drug to
the tumor cell okay so one of the

typical process is we do this kind of
injection right administrate

Dmitri
via nanoparticle so your brother vessel

by when you through the blood vessel
where the first thing you will see this

not a particle interact with this
protein right these kind of biologic

mature in your blood that's the first
thing

then the nanoparticle we're going to
circulate right through this blood

circulation that's a lot of thing right
once the dualist circulation you crude

so you are very hard all the way to the
olive lock vessel and these tableting or

eventually to the target area let's say
for example let's say you have problem

with a kind of legal problem okay you
have a little kind of tumor then this

and eventually will go to that area then
how there's not a particle exit right

the blood vessel into the tissue area
okay that's a lot of that's a lot of

kind of problem then once you the drug
release to the tissue then the next

problem is how this drug to penetrate to
the tumor by the tumor probably your

tumor is solid tumor right and the
concentration you're a lot of particle

were influenced how depths you're not a
party would have penetrated your tumor

right that's a lot of kind of issue in
your do is then even you consider that

right that means we less that we reach a
very tip of this kind of penetration to

your tumor then the next thing will
happens how this not a particle are

going to exit your to your tissue and
get inside a cell right that that means

how to sell object tumor cell uptake
nanoparticles and eventually we have

chocolate released right and we don't
want the drug will release before the

drug get inside the cell right we want
this drug inside cell then release okay

there are so many different kinds of
issues relevant to the drug delivery

from beginning all the way I I don't I
haven't seen anyone have done so

listicle II that means from her
beginning but you inject your kind of a

drug delivery and all the way to your to
your target area and release it and

after you release actually you also want
to lease nail up some nanoparticle can

read of your body okay so all these kind
of thing relevant to enhance how to

has the drug delivery to a tumor right
all these reissues every every part has

certain kind of challenges okay so today
I'm going to mainly focus on the

cellular optic and intracellular
trafficking okay

that means we as we consider all the
those issues has been solved

excuse me and we want to see how the
cell right getting inside the tumor

right that's I'm sorry how the
nanoparticle inside the tumor cells

right this slides tell us the basic
pathway right a typical pathway of

cellular uptake
of those nanoparticles so if you have a

very large particle let's say you have a
micron size particle typically the cell

will do the phagocytosis right to uptake
the nano particle this particle typical

are big okay and if you party will go
smaller you will see this kind of micro

pinocytosis and even all the way you
have a current dependent and the

receptor depend mediate kind of
endocytosis or either way if you have a

very small particle for gaddama water
particle right it's ion actually can

directly potentially sue your membrane
getting inside itself okay so I'm going

to focus on receptor mediated that's the
main area right now for this knowledge

or delivery system right we want coding
differencing on the cell right those

cell have some different type this type
of knowledge party will have different

type of ligand and the ligand will
interact with the receptor on the cell

membrane right we sue this kind of a
receptor mediated endocytosis right to

let the cell uptake nanoparticle these
are typical impact right for the

nanoparticle property right on the cell
object but we have seen lots of research

in both experiments and the modern
simulations okay so in terms of

nanoparticle
what other thing we can think about is

not a particle size no doubt right okay
think about a big not a particle small

particle right that's a that's one other
thing we have studied a lot and you if

you look in the integer there are so
many different types

work on that okay and the tech listen we
can think about is now the particle

shape okay that's a lot of very obvious
probability we can think about that

right like a severe cube raw triangle
right okay and the third part is like

targeting ligands that means we have
different type of targeted leggings on a

cell membrane
on another particle sorry now the

particle and how long on a particle will
be better interact with these cells and

relevant to this one is like a surface
chemistry

okay surface chemistry and our state is
about the composition that means we have

a different type of another particle
most we focus on the biological based

biologic material based nanoparticle
right these the reason is we want to

enhance the bioavailability will selves
but we also see lots of inorganic

nanoparticle like go right Seaver for
these type of drug delivery systems as I

said before right I mainly focus on
modeling simulations okay so let me just

give you a very brief kind of
introduction about the computational

modeling and also computational methods
I have used in this type of studies okay

so as I said before many folks on the
nano particle interacts with cell

membrane all right the cell membrane is
the majority of the cell membrane is

made of a phospholipid okay it's like a
bilayer lipid bilayer lipid and of

course you have these kind of
transmembrane protein okay and the

majority part as I said is like lipid
okay so this is a atomistic structure of

the t.o.p see that one of the
phospholipid and if i put them together

right try to make a patch of these cell
membrane get the the cell membrane can

be made of this d BD t OPC which with
all auto mystic models that means i

collect them in terms of atoms okay and
one by one okay and these type of

simulations based on all atoms okay
this type of summation actually give you

very much detail very detailed how those
each atom right move and how the not a

party will interact with the sale memory
okay but this type of simulation also

cost a lot of computational resources
okay so we want to reduce the

competition resources meanwhile we want
to maintain some kind of features right

from the simulations okay so we try to
use a lot of way that we call the core

screen MD simulation so the core scream
the assimilation idea is very simple

right instead of I show this Auto mystic
lipid molecule I group a certain number

of atom into a super B okay if you look
at here right that means I group this

part right as a one bit okay and I have
a lot of bead and you can see this is

the one of the you can say this is a
tail this is a head and this is a two

tail okay and I group those atoms into a
super bitch okay so then you can imagine

maybe this at this kind of a do PC
molecule is made of 200 or 300 atoms

right if I do the core screen I can
reduce the number of atom to a number of

a few number of big beads okay that will
be increased the computational modeling

simulation efficient a lot right so
that's a lot of kind of representation

I made of these across screen MD
simulations right this is the kind of

very cause MD model okay for the lipid
system and the computational tool we

have used for this type study one of the
solving the free call screen model and

of course we have done a kind of solvent
quarry model also okay and we also have

done lots of these dissipative particle
dynamics

okay so post them we can consider as a
molecular dynamic simulation I guess

lots of you have heard of that right
okay I suppose all of you heard of the

molecular simulations
if not okay I can give you a very short

an introduction of MD simulations so MD
simulation is a computational simulation

techniques that allow us to predict the
time evolution system interacting

particles so the particle can be Adam's
right can be molecules can be granules

that means that can be a big particle
can be a small group of atoms right so

the two thing for the MD simulation okay
one of the thing is when you consider

the the particle kind of initial
conditions okay side of a set of initial

condition for these particles that means
you need to tell me the initial

positions right and what is the velocity
for all the particles okay then the most

important thing for this first step is
we need to find a good as a suitable

inter-terminal potential to describe the
interaction between those atoms okay for

example in this case I just mentioned
that right I have these kinda super B's

right so how these silver beads interact
with each other okay so that's through

kind of inter Tomic potential right and
once we have these first step down right

we can go to second step the second step
is solving the the system right the

involution system in times can be
followed by solving a set of classical

equation of motion okay
in this case is M D it's kind of

Newton's second law okay very simple ma
equal to F okay the substitute I means

the number the ice particle atom right
and once we have the acceleration for

the lab particle based on initial
condition and the initial velocity we

can find the next step right velocity in
position

right as time goes on we can march on
march on then we show that how the atom

or how the system involved with x and
Allah last thing I'd mention here is the

force actually is relevant to your
potential right that revenue

inter-terminal how you choose the inter
time

or how do you define entertainment
potential that's very important and

that's most time we needed to according
to the real physical phenomenon okay

when you develop a kind of entertainment
potential okay

we want we want those potential actually
can reproduce the physical meanings

right physical behavior of those systems
so let me give you a little example a

small example about inter Tomica
potential right so this is the one of

the model I choose for similar soft nano
particle okay so for the nano particle

and the soft and our party was made of
in here it's made of kind of surface

here and the surface is meshed into kind
of triangle you can say triangle mesh

and each triangle mesh you have these
kind of particle right this particle and

the particle will form a triangle okay
and the particle particle they are

bounded through this bomb right and
these two element let's say you have a

two triangle this to this triangle this
triangle they have kind of you can say

bending right I want to show the
flexibility how the particle deform then

I have to consider the two adjacent okay
triangle can paint right that means to

change the angle between them okay so if
you if you take all these information

okay into the into account but we will
have these type of potential right the

perennial includes bound get into the
area okay that means I want to control

the area of the nanoparticle mean why I
want to also control the volume of

nanoparticle okay and also I consider
bending the bending as I mentioned that

is like how these adjacent adjacent
triangle right behave

this type of bending right that means I
need to control the angle between them

and this is a lot of model for the lipid
membrane okay

for for simplicity
in this case here I used actually this

week called three five five kind of
lipid molecule I can do further right if

I can if I want to simplify the model
again or even cause I can do a three B's

right I have a 1 K 1 1 hat and a two
tail and of course we know the tail ok

the tail of the lipid molecule is
actually hydrophobic okay and the head

is a hydrophilic ok and the potential
for this kind of membrane we can have

repulsive force hydrophobicity bond pain
all these type of things

ok I'm not sure here that was details
and all these parameters KS k k VK or

those parameter actually from the
experiments okay or either way you can

you can calibrate based on the current
MD simulation for those systems right

you can have these parameters from
experiments right they make a model

compared with that or either way based
on the current data from MD simulations

ok those parameter has been studied for
nanoparticle interact with the cell as I

mentioned before right one other thing
is another particle size this also been

done a lot ok
now the particle shapes ok they also has

been done a lot ok I have a very simple
question for you guys okay for another

particle shape okay okay when we have
these severe model okay and you will see

through this type of interaction you
will see the another particle will be in

a cytosis through this member right for
this a now the particle shape with rod

okay
KO tell me typically what type of

rotation you will see okay when another
particle rod shape like a particle in

tag with the cell membrane why you will
see this kind of rotation right let's

say I just randomly choose an angle
whatever

okay now rod
with the cell membrane right and

typically how the nanoparticle is now
rather will be interact with this with

the cell okay these things we have never
seen from experiments viewpoint is very

difficult this is a very dynamic process
right and when we see this resulted from

experiment we work we just know I we
couch your cell

we put a nanoparticle right with the
cell and after a few hours we just

checked how many amount another particle
object by itself but we don't know

Harlen a lot of particle so the member
getting inside right so simulation can

tell us this type of evolution right
dynamic evolution how long other

particle interact with the same membrane
getting my cell yeah so my question for

for you here is if I have a now rod
right instead of nano Saphir

okay how this now rod away in tack was a
member just try to from the energy

viewpoint what what happens you were
just directly penetrate this room or

there's another particle will lay down
then then get inside they have some

other motions service potential okay of
course that that ever right but if let's

say if we just put aside a surface
potential let's say we have a love

surface potential how is he

okay so based on current simulation have
done by other scholars in cream myself

right so most time if you have another
particle like Raja and a particle in

that way cell memory that not a particle
the matter would kind of angled another

particle eventually will lay down first
okay lay down for that that's pretty

easy to understand from the energy
viewpoint right you increase the contact

area you increase the adhesion force
between them right then after you wrap

by the membrane let's say you remember
wrapped another particle the another

particle will totally wrapped by
membrane right and you want to pinch off

right the next step is you want to pinch
off the pressure off when I try to

picture of actually the metal party will
lay up again okay so the nightfall go is

get inside right lay up I'll get the
foam laying down right once you wrap it

by the membrane and that party will try
to lay up again and then you pinch off

okay so that's that's also kind of
interesting phenomena that's from the

energy viewpoint I think is it easy to
understand the reason if if you if you

try to pinch this way you have a loss of
area to pinch off right okay that's

caused a lot of energy but if you try to
pinch this way that's that means you

pinch on tip that's a very easy to pinch
off separated for your membrane okay and

also we have a seeing a lot of study
working on the surface chemistry right

now the party surface chemistry we
coating with different thing right like

a protein polymer all those type of
biological materials try to enhance or

either way prevent some kind of behavior
between Sarah and nanoparticle okay and

also we have see lots of study for the
micro environment effect as I mentioned

before right when we put the drug in the
in your body most time you will see the

drug actually in a block right on the
plot condition so blood actually you

have a flow right the blood flow after
you have a velocity that's a shear that

will generate a shear force
right so how does shear force in tax

okay cause the inference then on a
particle right intact with the sails

member or sail okay that's a lot of kind
of thing we see a lot of studies these

typical simulation based on the largest
ghost vision in a way measure match free

or either way it's based on these kind
of final analysis okay so what else can

we study okay same is here we have to
see most of them right for for

nanoparticles we haven't see lots of
them

what type of thing do you think we can
make a contribution here okay based on

the knowledge part Eagle property right
and how the nanoparticle intact with the

sails

okay so I think all of us haven't seen
this type of thing

right how those virus can interact with
the cell okay so we will have a virus

the virus typically behaves very soft
you agree very soft and kind of particle

right solve the particle right comparing
with those in organic another particle

okay we made of less than made of gold
made of silver all those things right

they are very stiff yeah so the question
is how those material or say particle

stiffness right influence the uptake
that means if I have a if I have a

particle made of hydrogen right those
kind of a yawns module stiffness very

comparable to your cell membrane right
okay instead of you have a particle made

of gold or made of polymers numbers very
very strong material stiff material

right how these particle stiffness right
influence the cell uptake okay we have

seen a lot of kind of engineering
fabrication right for general rate

different type of stiffness
nanoparticles right sometime another

particle was stiva some not a lot of
soft but we have many many times with a

clock techniques wall over here is
developed by dr. Shi

okay you have these type of water and
you have a P PLGA that's a kind of

polymer okay and you can have coating
with different type of coal right this

call and the coil is likely you can say
it harder particle is a hard hard call

but encoding with this lipid and of
course here it actually you are putting

inside a water right okay between the
collar and the shield that will make the

party were pretty soft okay

so before I'm talking about okay show
some results how these nanoparticles

difference inference table take right I
would like to give you a few of these

kind of studies I haven't done in a few
years

okay this picture actually show how
these coding patterns right I have a

call let's say I have a particle
nanoparticle core and the coding with

the different patterns of polymers okay
and this polymer you can imagine a

polymer can have hydrophobicity and Joe
hydro sometime is a hydrophilic

sometimes just hydrophobic right so I
have these tighter pattern then you have

a B pattern ABA is the hydro typically
we say hydrophilic and the P is

hydrophobic you have these kind of have
a feeling polymer and you have a

different you changing with different
coding patterns right and you will see

how this nanoparticle penetrates through
the membrane okay so this pattern

actually were influenced you're entering
force of this nanoparticle get inside

the cell and from here we can see this
PA pattern okay had a smallest or the

minimum force the smallest force to get
inside a cell okay and this type of

simulation okay we can provide some kind
of guidance experiment guy experimental

guidance for your extreme world right
provide the guideline right how we

fabricated nanoparticle and another
party we can easily getting inside the

cell right to for fear drug delivery
system and also we have this doula

simulation to mimic the drug delivery
system process here you can consider

this in all sale the sale is a much
larger than this size here okay we do

not have not logically the computational
resources so we simulate the cell just

like a leper zone you can consider
Lebanon right and a lot of particle

interact with a cell and you actually
get an inside cell and eventually that

this nanoparticle will be dissolved the
shell and deliver the drug right inside

the party you can consider the drug
for the drug process and a lot of

interesting study we have done I think
in 2006 without real paper is a study

how we use these kind of two-dimensional
material right actually to extract or

remove the class show okay from your
cell memory okay so the class show level

actually relevant to loss of disease
right for example diabetes or or

relevant to the fat you have lots of
those if you have lots of a fat kind of

grease inside body the sale actually
have the cell membrane involve loss of

those cholesterol so we would ever want
to recur rid of those crest roast right

so one of the thing we think about is
mechanically we saw kind of remove these

crest rows so we made a model very
similar model right so this is the Qaeda

cell membrane and the same memory have a
loss of kind of lip lipid of cold and

lipid molecule and of course have loss
of those class shows and we we put a

kind of graphene right the graphene is
like two dimension materials and through

that membrane and we masu the member and
actually you will see this kind of small

okay crash the molecule will climb on
the surface of your graphing and

actually you will get rid of those crash
all right through these interaction and

here is the wall of the movie it can
take a look

you see this nanoparticle classroom
molecule actually climb on the surface

of the graphene and also we have we have
done all the kind of simulations right

to study these lot of particle shape in
fact and the rotations those types of

things okay okay the last few slides
okay I would like to show how these

nanoparticles difference right influence
the contact process okay this is this is

a one of the thing we we published
recently and we study a two different

data particle this particle is riveted
hot this particle live is soft right you

will see the call and you have coating
who is the kind of our team or something

like that and this is just a single
layer polymer and this one we have a

core and we have a gap right then you
code in some kind of a polymer okay and

that's make the particle very soft and
if you look at here you will see these

hot a party who are easy to wrap okay
and these solve the particle very

difficult to wrap okay you can you can
try by yourself I I try before sometimes

you can success sometimes you cannot so
one of the example when she says and try

to try to wrap let's say you wrap a
harder particle let's say Apple right

and you have a lot of soft particle
let's say I have a small balloon okay

and you try to use a very larger broom
right to wrap them okay pose and you

will see if you try to wrap these small
balloon that's a soft a softer one right

it's very difficult to wrap you can
easily wrap the hard one right like an

apple okay you can try by yourself okay
and also we we study the cooperative

entry of the tuonela particles with
different stiffness and interesting

happens is if we have a hard particle
okay

the particle
inside the member actually is one by one

okay they sue the party so we remember
and one by one but you have a softer

particle these party will choose to get
inside sale at the same time okay so I

haven't I haven't done more okay I tried
it down more okay let's say I have a

group of nanoparticle okay not just one
- okay even larger number of body we'll

see what happens but I list from here I
see if I have a softer one okay

I have harder one is soft this this
hollow one try to get a member in one by

one but if it's softer one you sometimes
just get it membrane simultaneously

right together okay and here it's a lot
of kind of a simulation I'm calling a

walk on and we just submitted paper and
this is a I want to study the shape

effect for this deform of articles okay
there are lots of work have been done

about the shape right but we made when
those papers dealing with the shapes at

that time they couldn't see the particle
isn't non-deformable with rigid okay so

this time I'm trying to consider solve
the particle let's say I consider with

from the rod shape all the way to the
Saffir right based on based on the

ratios right okay isomer ratios and the
onliest particle considered are the same

volume okay that means this party will
have a same volume but only with a

different kind of a spur ratios and USC
when the particle is solved okay

actually the particle will be pain okay
deform with this member okay that's a

very interesting phenomena which is the
different from these stiva particle

okay I should have provided comparison
side-by-side one yourself that one is a

heart okay there'll be more interesting

I'm going to jump these things okay
so maybe give me five more minutes let

me wrap it up I have one thing I want to
discuss a little bit more it's a we have

already seen most of the current
research working on another particle

interact with cell are based on this
kind of what we call the passive now

that particle so the particle itself
okay doesn't move okay that's typically

just uptake by the member okay so what
what happens right if we consider

particle actually is active that means
the particle itself has a motion have

some energy to to rotate or
we're transport right see what happens

okay so these things actually give a lot
of information about activity now the

particles we have a see these kind of
magnetic another particle by getting

inside a cell and we use a magnetic
field right to general the either way

generally heat or either way generally
the kind of rotation right the other

rotation actually can wrap the cell
membrane but if you wrap the cell

membrane the cell will be die okay and
also we have see this type of staying

food plot clot dissolving right we
deliver a lot of particle here these are

magnetic another particle then you
rotate they once you rotate you will try

to accelerate the dissolve a blood clot
mechanically and I show a few

simulations okay let me just bring all
of them together so that will be easy

okay so these slides tell us very simple
kind of idea right if we have this

nanoparticle right as she's rotating one
is an incline rotate one is all the

plane rotate actually you will have
different behavior by interact with the

cells or cell membrane if you actually
rotate was in plane that means axial

rotation okay you can easily penetrate
through the membrane or if you have a

auto plane rotation that will cause a
damage huge the damage of your membrane

right and for example if I have this
type of design okay I can generate a

kind of a channel right on the cell
membrane and this channel hopefully we

can use this channel to enhance the drug
delivery okay so you can screw the

channel the channel came through the
nanoparticle came through the channel

get out of the cell or either way the
latter part of our cell can get inside

the cell okay
and based on this idea we we general

lots of different kind of connections
between these cells actually you can use

in this channel like to exchange this
information bit from A to B right

largest these small particles actually
you can do a larger particles let's say

I can hopefully I can use this technique
to transport DNA for one cell to another

one right if I one of them is a it's
kind of disease the cells right Allah

low and he'll sell I can use those kind
technique to transfer some information

or DNA information from one cell to
another one that's Q Allah lower right

these type of ideas

okay and the last thing I want to show
here is we have see a lot for

chemotherapy that means we use those
chemical behavior another particle to

kill tumor cells right so horrible if I
design a nanoparticle and a lot of

particle not only deliver those chalk to
a chemical drug to kill the cell

meanwhile this nanoparticle can be
rotated okay that means if the lab can

rotate I can exert a mechanical force on
the sails right and I hope this

mechanical force can disrupt the cell
membrane okay I accelerate that process

that means I can use chemical property
and also I can use mechanical property

of those nanoparticle right to kill the
cells that'll be great

right so I've made a lot of simulations
if I have another particle made of in

this case made of raw kind of a co shape
and I attach to the nano particle on the

cell membrane and that the nanoparticle
rotate and the actually you will see

depend of course depends on your kind of
attack attachment strains right between

the cell and nanoparticle that
eventually you will see this kind of

rupture behavior of a cell membrane and
of course we do a little bit more

simulation about different shapes of
nanoparticles and you will see this L

shape and the rod shape another particle
even better to mechanically rub the cell

membrane and right now we are working on
experiments ok we hope we can have some

experiment results coming soon to
validate these kind of models ok and

this is the last movie I would like to
show you then I'll stop here

yeah
so if I rotate nanoparticle along this

diagonal axis and you will see this kind
of ruptures right and if if if we can

design by three dimensional a particle I
think that will be better okay and the

challenging part right now for this kind
of experiment work is how can you rotate

in another particle along the desired or
target axis right that's a big challenge

for us okay the fabrication and the the
other kind of thing is not very

challenging okay so let me I just stop
here okay thank you

you may hear my simulations mice
invasion is a go 200 nanometer maybe

let's say maybe 10 200 something just
for Nana one other particle I use cross

screen model all all those things are
based on course cream dissemination

not-not-not ought or atom MD simulations
close agree so I think the nanoparticle

I have for that model is like maybe
three or four hundreds a kind of kind of

big atoms okay he said you can say big
beat right instead of atom

okay I think that's your your hundred
percent right so wait the way I did for

the course Queen MD model right I based
on the MD simulation not for first

principle calculations you can of course
you can do the simulation from first

principle to get a mechanical properties
right and try to fit that or you choose

all atomic simulations I the way I did
is I used those current very matured

developed all atomic scale simulations
to match a few important parameters

right for micro screen models okay so I
develop a cross screen model based on

those potential forms I have a certain
kind of parameter to optimize right when

I when I autumn eyes I will rat I will
try to match those properties by from

course query model to my domicile model
that's the way I did

okay that's that's a very interest
question okay the I I just happen to

make a model I try to make a model from
from altima simulation to the quarry

model the one is simulation you see the
call screen simulation right

I try to similar something let's say I
try to make a model from from the

autonomous model of Agravaine right
interact with this classroom molecule

okay and I I see that the cross draw
molecule are very easy to attach to the

surface of the graphene right
if of course when I see Melissa

Malaysian I put these class show in a
memory structure the membrane is a kind

of liquid molecule the structures
typical audio Dana classroom okay a

little bit larger than that and I think
the reason is the interaction the the

hissing force between the classroom
molecule and graphene is a stronger than

the DP this kind of lipid molecule
between the graphing and also a lot of

thing is this lipid molecule people call
small okay it's easy to get rid of those

structure climb on the surface by
instead of these lipid molecule and then

live in the molecule you have it you
have a we have a tail right they tried

to stay together this tail or
hydrophobic try to stay together okay

but these equestria not that that's my
understanding

I mean that that I I discussed this
project that maybe two years ago with

one of my colleague from the computers
from the chemistry and he tried to do

that but it it is very difficult to set
up with those kind experiments you have

this kind of membrane and you have put
the you have to put this cholesterol

more cholesterol inside right and you do
this kind of penetration and protein

process we haven't success yet but I
think is a very interesting to look into

we haven't look at that

crowd party there are two two modes one
is the nanoparticle can listen and a

particle can attach on the surface right
III know your point so if the particle

is a fully good info in the cytosis by
the cell that means then you rotate

that's not a party just loaded inside
the cell that's very difficult to to

break so what we do is we hope this not
if you try to culture the cell right you

put another particle and we with
definitely want a matter time control a

time how much time you need to to let
the particle interact with cell right

then we we mirrored that right time sayo
then apologies are attached on the

surface a membrane then you rotate

yes yes

okay so there's a there's a two
parameters one is finding bonding

strains okay Bonnie's train time is
relevant to the ligand and the receptor

on the cell membrane right so there's
that that also depends on the strength

and also depends on the density how much
kind of lipid you put on the on the

nanoparticle that's one of the parameter
our other parameter is a rotating

frequency that means how fast you rotate
get that that's also can be controllable

okay so you can imagine if I if I if I
rotate very fast okay and that that will

be us see in this case you will see no
matter no matter are in this case see no

matter what's your rotating frequency
right if you have a very high strength

okay actually you will see there always
have the damage so the rotating

frequency I know this one in this case
right you can control the magnetic

automotive magnetic field then control
the rotating frequency we have see those

things before for from an experiment
viewpoint but we haven't done for the

real application not a particle with
cell member but we see how to control

the porteño frequency a stall means the
rupture that the the cell is damaged and

these these are these are so close means
they're not always a perfect

oh let me see another vice versa vice
versa sorry rice was okay

that's definitely true and that's that's
one of those things we are well actually

right right now we are working on we
want we want to introduce multiple

nanoparticle at the same time not just
single particle right if you do a single

party no doubt for this stimulation you
never see those kind of Gration but if

we do experiment see very difficult to
control just one particle inside

remember right inside the channels
whatever so we will study those

collective behavior definitely if you
have another particle right let's say is

hydrophobic right no doubt if you put
them together if we just randomly

distribute eventually they try to
aggregate together that's their very

true and that we want also want to see
how those aggregate cluster interact

with nanoparticle if you have a small
different way right if you're a larger

wall see what happens so that's that's
definitely kind of thing we are looking

into right now yeah thank you

aye aye I agree I read a couple of a
review paper okay and published in

nature in recent years so one of the
papers saying they did do lots of a kind

of statistic kind of analysis and
collect all those papers in your field

they say right now is around point 7
percent of those administrators are

drugged right will be go to your tumor
cell point seven percent that's low okay

so that's relevant to the one on the
slide I mentioned that they have a

several battery a several kind of
process way from the from the injector

the kind another particle all the way
plot of circulation and to your tumor

cell optic all these process actually
will be try to clean out of you another

particle for your body by your different
organs right different interactions how

we to improve those interactions how we
improve that will be improve those

efficiency okay
deliver to the tumor cell that's a very

big challenge 0.7% that's that that's
kind of a paper I read before it's very

very low then we can imagine that thank
you