Hydrophobic Mismatch Controls the Mode of Membrane-Mediated Interactions of Transmembrane Peptides.

Oleg V Kondrashov,Peter I Kuzmin,Sergey A Akimov

doi:10.3390/membranes12010089

Oleg V Kondrashov, Peter I Kuzmin + Show 1 more

Open Access

https://doi.org/10.3390/membranes12010089

Copy DOI

Abstract

Various cellular processes require the concerted cooperative action of proteins. The possibility for such synchronization implies the occurrence of specific long-range interactions between the involved protein participants. Bilayer lipid membranes can mediate protein–protein interactions via relatively long-range elastic deformations induced by the incorporated proteins. We considered the interactions between transmembrane peptides mediated by elastic deformations using the framework of the theory of elasticity of lipid membranes. An effective peptide shape was assumed to be cylindrical, hourglass-like, or barrel-like. The interaction potentials were obtained for membranes of different thicknesses and elastic rigidities. Cylindrically shaped peptides manifest almost neutral average interactions—they attract each other at short distances and repel at large ones, independently of membrane thickness or rigidity. The hourglass-like peptides repel each other in thin bilayers and strongly attract each other in thicker bilayers. On the contrary, the barrel-like peptides repel each other in thick bilayers and attract each other in thinner membranes. These results potentially provide possible mechanisms of control for the mode of protein–protein interactions in membrane domains with different bilayer thicknesses.

Highlights

Various vital cellular functions are catalyzed by membrane proteins
To analyze the dependence of the transmembrane domain (TMD) interaction on the elastic properties of the membrane, we used two sets of elastic moduli, approximately corresponding to liquiddisordered and liquid-ordered phases: splay moduli Bd = 10 kB T, Bo = 50 kB T [46,47]; lateral stretching moduli Kad = 133 mN/m, Kao = 665 mN/m [46,48]; tilt moduli Ktd = Kto = 40 mN/m [41]; the moduli of the Gaussian splay were expressed via the splay moduli as KG = −B/2 [49] ( the Gaussian splay contribution is constant for the boundary conditions in Equations (4)–(6)); the twist moduli were estimated as Krot = B/2 [35,37,39,45]
In order to evaluate the type of average interaction under low TMD concentrations, one should calculate the Mayer’s first cluster integral [50,51,52]:

Summary

Introduction

Various vital cellular functions are catalyzed by membrane proteins. The most complicated processes require the concerted cooperative action of several protein molecules, synchronized both spatially and temporally [1,2,3,4]. The tendency of the system to minimize elastic energy represents the driving force for the lateral sorting of proteins between membrane domains of different thicknesses; it is referred to as hydrophobic matching [18,19] This type of sorting is very sensitive to even tiny differences in the bilayer thickness and the length of the TMD. Cellular rafts may not be the result of global phase separation in the plasma membrane but rather of the local phase separation induced by membrane proteins in their immediate vicinity, e.g., by the wetting mechanism [30,31,32,33] This leads to the idea that the membrane must have a huge number of domain types, approximately equal to the number of membrane protein types. Protein–protein interactions in membrane domains each other to cylindrical These results potentially provide a possible with different bilayer thicknesses. Mechanism for the selective tuning of protein–protein interactions in membrane domains with different and bilayer thicknesses

Methods

Results

4.4.Discussion