The asymmetric plasma membrane-A composite material combining different functionalities?: Balancing Barrier Function and Fluidity for Effective Signaling

Abstract

One persistent puzzle in the life sciences is the asymmetric lipid composition of the cellular plasma membrane: while the exoplasmic leaflet is enriched in lipids carrying predominantly saturated fatty acids, the cytoplasmic leaflet hosts preferentially lipids with (poly-)unsaturated fatty acids. Given the high energy requirements necessary for cells to maintain this asymmetry, the question naturally arises regarding its inherent benefits. In this paper, we propose asymmetry to represent a potential solution for harmonizing two conflicting requirements for the plasma membrane: first, the need to build a barrier for the uncontrolled influx or efflux of substances; and second, the need to form a fluid and dynamic two-dimensional substrate for signaling processes. We hence view here the plasma membrane as a composite material, where the exoplasmic leaflet is mainly responsible for the functional integrity of the barrier and the cytoplasmic leaflet for fluidity. We reinforce the validity of the proposed mechanism by presenting quantitative data from the literature, along with multiple examples that bolster our model.

Keywords: diffusion; fluidity; lipids; membrane asymmetry; permeability; plasma membrane.

FIGURE 1

Sketch of the plasma membrane, with the exoplasmic leaflet drawn in red, the cytoplasmic leaflet in green. Dark red and light red indicate basolateral and apical membrane in polarized cells. In our model, the key function of the outer leaflet is constituting a permeability barrier, whereas the fluidity of the inner leaflet is important for forming a dynamic matrix for (i) enzyme‐substrate reaction, (ii) dispersion of signals, and (iii) the association of peripheral membrane proteins or protein domains. See main text for more details.