Biological membranes and peptide pores

Translations: FR

The interaction of cell membranes with the molecules adsorbed on their surface and the way in which the incorporation of these molecules takes place is still poorly understood. We are interested in antimicrobial peptides that form the keystone of the innate immune system of multicellular organisms. Basically, these peptides make membranes permeable by forming pores in them. Their universal presence in the animal and plant kingdoms, their non-specific and broad-spectrum action as well as their very elementary structure suggest a mode of action according to physical mechanisms that are also very general and universal. We have addressed this problem through patch-clamp experiments (consisting in measuring the transmembrane ionic current while a given voltage is applied) couipled with neutron reflectivity. In particular, we showed that pore openning exhibits a slow dynamics typically observed near the glass transition, which could be governed by concentration fluctuations of peptides on the surface as it is predicted by the RSA model (“Random Sequential Adsorption”). We are also interested in the thermodynamics of pore opening as a function of temperature and applied voltage. Our results allow us to propose a new physical mecanism where adsorption of peptide and the electric field both contribute to membrane bending. With this mecanism the main entropy cost to pore opening comes from an “exclude area” effect for lipid translation.

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The equilibrium between peptides (here symbolized by the small cylinders) adsorption and insertion within the membrane to form a pore depends on the thermal energy and applied field.

Incidentally, it is amusing to note that these pores behave like diodes allowing the electric current to be rectified (in a way similar to a ratchet/pawl wheel operating at a molecular level and that this is made possible thanks to thermal energy. These systems are known as “brownian ratchets” .

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