My name is Gianluca Marcelli, I'm a Lecturer in Bioengineering at the University of Kent.
Today I am going to talk about my research in the mechanical properties of red blood cells.
It is very well known that red blood cells transport oxygen from the lungs to the tissues
and in doing that they have to go through very small capillaries.
The red blood cells contain haemoglobin proteins, these proteins can bind to oxygen and that's
the reason why red blood cells can transport oxygen.
Haemoglobin is also responsible for the red colour of the red blood cell.
In terms of size, the red blood cells are very, very small.
If you think of human hair, for example, the thickness of the hair is three times the diameter
of the cell.
So, again, the red blood cells are very, very small.
As I mention, the red blood cells have to transport oxygen from the lungs to the tissues,
and in order to do that they have to squeeze through very small capillaries which are smaller
than the diameter of the cell.
So in order to achieve this, the red blood cells have to have remarkable mechanical properties.
In particular, the red blood cells have to be strong, rigid enough not to break down
and they have to be soft enough in order for the cells to deform within the capillaries.
If you look at the red blood cell membrane, the red blood cell membrane is made of lipids and proteins.
And it is this molecular structure that provides the remarkable properties to the red blood cells.
In particular, the lipids form a bilayer which provides, to the red blood cell, the resistance
to bending.
The proteins, in particular, the spectrum proteins form a network, a scaffolding under
the red blood cell membrane.
And this scaffolding provides the resistance to change in shape.
So the molecular structure is very important for the mechanical properties of the red blood cell.
In fact, when the molecular structure goes wrong the mechanical properties can be different
and then the cell function can be affected.
You can think of sickle-cell anaemia, for example, where abnormal haemoglobin proteins
make the red blood cell more rigid and provides, to the red blood cell, a shape which looks
like a sickle.
These abnormal cells can block the blood flow and can cause the people carrying the disease
to have pain attacks and anaemia.
So it is very important to understand the link between molecular structure of the red
blood cell and the mechanical properties, because the mechanical properties affect the
function of the red blood cell.
Bioengineering is the discipline, the study of the human body and in general the biological
systems as machines.
And in particular, bioengineering studies the mechanical properties of the red blood
cells, and tries to link the molecular structure of the biological systems to the mechanical
properties of the system itself.
But how do you measure and how do you assess the mechanical properties of a material?
You can take a piece of the material and you can apply a force.
The force will deform the material.
The bigger the deformation, the softer the material.
The smaller the deformation, the stronger and more rigid the material.
So you can perform these experiments where you take a piece of the material and deform
it through a force.
And you can do the same thing with red blood cells.
For example, you can take a red blood cell, take a little pipette and suck a piece of
the membrane from the red blood cell.
The suction of the pipette will form a tongue of the membrane inside the pipette.
The length of this tongue within the pipette can tell you about the mechanical properties of
the red blood cell.
This is fine but the red blood cell is very small and is very soft.
So the interpretation of these experiments sometimes can be very difficult.
So you need to do something different.
You need to do something more.
That's exactly what we do with our research.
In our research we developed a computer model of the red blood cell.
In this model we represent each part of the cell as a simple bead.
We use so many beads to form the entire membrane and these beads, very importantly, are connected
through springs.
If you choose rigid springs then you ended up with a cell model which is very rigid.
If you soft springs, you ended up with a cell model which is very soft.
So, choosing different springs can provide different mechanical properties to the cell model.
Once you have the model you can reproduce experiments on real cells.
For example, with our model we can reproduce the experiment of the pipette where you suck
a piece of the membrane of the cell.
We can do exactly the same type of experiment with our cell model.
The moving presentation shows how to suck a simulated pipette a piece of the membrane
of the cell model.
We can choose different springs and the goal is to achieve a length of the tongue within
the pipette which is similar to the length to the tongue of the real cell.
When they match is achieved, then we can say that the mechanical properties of the cell
model are the same as the mechanical properties of real cell.
In doing that we need to go through the process of tuning the springs.
So we can measure indirectly the mechanical properties of a real cell using the cell model
by going through this process of tuning the springs.
We can reproduce a different type of experiment where the fluctuation of the red blood cell
membranes are observed.
Again, on the left hand side you have the experiment and on the right hand side you
have the simulated experiment.
We go through this process of tuning the springs and when the undulation and fluctuations from
the simulated model are the same as the real experiment, then we can say that the mechanical
properties of the cell model are the same as the mechanical properties of the real cell.
So, again indirectly we can measure the mechanical properties of the real cell using the cell
model, and going through this tuning process.
Currently, we are taking this research further.
We don't want to go through the tuning approach but we would like to predict the springs directly
from the simulation of a patch of the membrane of the cell.
We simulate, at a molecular level, a patch of the real cell using these molecular simulations.
These molecular level simulations allow us to predict the values of the spring which
we can introduce in the cell model and then we can repeat experiments and see whether
the simulated experiments directly match the experiments on the real cell.
This molecular simulation will allow us to relate the mechanical properties of the real
cell directly to the molecular structure of the membrane of the red blood cell.
More importantly, we'll be able to see how a normal molecular affects the function of
diseased cells.
Once we have achieved this we can propose to biologists how to fix the molecular structures
of diseased red blood cells.
The work I've presented today is also down to the collaborators I have around the UK.
Specifically, Thomas Hunt from the University of Kent, Jemma Trick and Chris Lorenz from
King's College London, Peter Petrov and Peter Winlove from the University of Exeter.
Thank you very much for your attention.