Artificial cell membranes boost medical research
The cell, an enormously complex unit of all known living organisms, also called "the building block of life", is the smallest classified unit of life. Understanding the components and functions of cells are essential to understand the mechanism of life. After all, the human body contains about ten trillion cells...
The outer shell of the cell is called the cell (or plasma) membrane. Any kind of communication between the cell’s interior and the surrounding environments needs to pass across the cell membrane, in one way or another. Therefore, the components of the cell membrane – mainly constituted by lipids and membrane proteins – are crucial for the functionality of cell communication. This makes membrane proteins to one of the most important classes of drug target molecules, since a common way of drug function is to let a drug molecule interact with receptor molecules (mainly proteins) in the membrane to alter the cell’s behavior.
The picture illustrates a cell with its cell membrane, and how molecules construct the cell membrane in detail. The cell membrane is basically built up by a lipid bilayer with embedded proteins (membrane proteins).
Impossible to study
One of the major bottle necks of today’s drug discovery process is the lack of robust methods for studies of the interaction between membrane proteins and potential drug candidates, preferably while the membrane proteins are kept in a near-native state. The problem lies in the very delicate nature of membrane proteins. They are e.g. easily denatured when they are removed from the cell membrane and adsorbed on e.g. hard surfaces, which is a common strategy of today’s kinetic interaction studies. Another problem is also the low concentration of certain membrane proteins, making them impossible to study with existing techniques for kinetic interaction studies.
New bioanalytic sensing technique
Researchers at Chalmers mimic and utilize processes within the cell membrane – called membrane fusion – in order to create new bioanalytic sensing techniques to improve the understanding of cell membranes and their interactions with various molecules, for instance, drugs and viruses. The aim is to facilitate efficient studies of interactions between membrane proteins and potential drug molecules, while avoiding the problems mentioned above.
One potential solution is to enable these kinds of kinetic interaction studies, while keeping the membrane proteins in a near-native state, similar to that within the cell membrane. Dr. Lisa Simonsson, at the Biological Physics Division, and her colleagues Dr. Anders Gunarsson and Dr. Peter Jönsson have successfully established a way to create flattened cell membranes, known as supported lipid bilayers, out of real cell structures. These bilayers provide an important key to understand cell membranes.
Better cell membrane models will improve the understanding of drugs’ function.
Supported lipid bilayers – a thin membrane made of two layers of lipid molecules – are artificially created by adsorbing lipid vesicles in solution to a solid support, which at a critical coverage burst and fuse producing a two-dimensional membrane. This is considered as a very first step towards the realization of a bioanalytic sensing technique for membrane protein-drug interaction studies in a near-native state.
The team made their first step
However, most supported lipid bilayers are simple. Dr. Simonsson wishes to investigate more complex systems that are more identical to real cell membranes. The team made their first step in that direction by successfully incorporating vesicles derived from real cell membranes, into supported lipid bilayers, using microfluidics. The team was able to move a bilayer, placed in the bottom of a buffer-filled channel, towards a set of cell membrane derived vesicles by syringing more buffer into the end of the channel. When the edge of the lipid bilayer reached the vesicles they ruptured and flattened.
By means of this technique, Dr. Simonsson and her colleagues know how to incorporate cell membrane components (proteins) into their artificial cell membrane structures – a profound problem due to the difficultness of handling membrane proteins without causing damage to them. By using a flow of buffer through a microfluidic channel, the motion of membrane proteins within the two-dimensional structure was controlled (spatial manipulation). This enables researchers to accumulate and separate out membrane proteins of e.g. different sizes, while keeping them in the natural environment of the cell membrane. This will potentially allow researchers to incorporate cell membrane proteins to such high local concentration levels that interactions between cell membranes and molecules can be studied with a microscope or other surface-based techniques.
This, Chalmers based, technique would, for instance, allow the pharmaceutical industry to perform enhanced testing of new drugs, which could fundamentally accelerate the quest to cure many diseases.
Dr. Lisa Simonsson, +46 31 772 61 09
Christophe Eléhn, Communications Officer, +46 31 772 25 46
25 april 2012
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