Lipid Dynamics in Membranes Slowed Down by Transmembrane Proteins.

Lisa Ebersberger,Sonja A. Kirsch,Alexandra Schambony,Tilo Seydel,Kristyna Pluhackova,Torben Schindler,Rainer A. Böckmann,Tobias Unruh

doi:10.3389/fcell.2020.579388

Lisa Ebersberger, Sonja A. Kirsch + Show 6 more

Open Access

https://doi.org/10.3389/fcell.2020.579388

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Abstract

Lipids and proteins, as essential components of biological cell membranes, exhibit a significant degree of freedom for different kinds of motions including lateral long-range mobility. Due to their interactions, they not only preserve the cellular membrane but also contribute to many important cellular functions as e.g., signal transport or molecular exchange of the cell with its surrounding. Many of these processes take place on a short time (up to some nanoseconds) and length scale (up to some nanometers) which is perfectly accessible by quasielastic neutron scattering (QENS) experiments and molecular dynamics (MD) simulations. In order to probe the influence of a peptide, a transmembrane sequence of the transferrin receptor (TFRC) protein, on the dynamics of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) large unilamellar vesicles (LUVs) on a nanosecond time scale, high-resolution QENS experiments and complementary MD simulations have been utilized. By using different scattering contrasts in the experiment (chain-deuterated lipids and protonated lipids, respectively), a model could be developed which allows to examine the lipid and peptide dynamics separately. The experimental results revealed a restricted lipid lateral mobility in the presence of the TFRC transmembrane peptides. Also the apparent self-diffusion coefficient of the lateral movement of the peptide molecules could be determined quantitatively for the probed short-time regime. The findings could be confirmed very precisely by MD simulations. Furthermore, the article presents an estimation for the radius of influence of the peptides on the lipid long-range dynamics which could be determined by consistently combining results from experiment and simulation.

Highlights

The interactions between lipids and proteins in biological membranes play an important role in e.g., cellular signal transport as well as the exchange of molecules or ions between the cell and the cellular environment
The question arises whether this slowdown can be attributed solely to the slow peptide dynamics or whether the presence of the peptides induces a reduction of the lateral dynamics of the lipid molecules
quasielastic neutron scattering (QENS) experiments and molecular dynamics (MD) simulations have been performed to study the long-range molecular motions within a DMPC membrane loaded with transferrin receptor (TFRC) peptides in transmembrane orientation

Summary

Introduction

The interactions between lipids and proteins in biological membranes play an important role in e.g., cellular signal transport as well as the exchange of molecules or ions between the cell and the cellular environment. In order to explain these discrepancies, Galla et al (1979) assigned the concept of the free volume theory (Cohen and Turnbull, 1959; Turnbull and Cohen, 1961, 1970) which originates from glass physics to membranes They assumed to observe a shaking of lipid molecules in their cage of neighboring lipid molecules in the short-time regime of QENS measurements. The first step of a long-range diffusive motion was thereby explained by the hopping of a lipid molecule out of its cage position between the nearest lipid neighbors into a neighbored vacancy created by thermal heterogeneities (Vaz and Almeida, 1991; Almeida et al, 1992) For many years this so-called free volume theory was able to successfully explain the discrepancies between the diffusion coefficients measured by microscopic and macroscopic methods, respectively. Doubts about the simple mechanistic interpretation of the free volume theory aroused, when realizing by MD simulations and experimental studies that molecular jumps into vacancies could not be observed and neighbored lipid molecules perform highly correlated motions over distances up to the nanometer range (Ayton and Voth, 2004; Gambin et al, 2006; Rheinstädter et al, 2008; Roark and Feller, 2009; Busch, 2012)

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