Degeneracy in molecular scale organization of biological membranes

The scale-rich spatiotemporal organization in biological membranes has its origin in the differential inter- and intra-molecular interactions among their constituents. In this work, we explore the molecular-origin behind that variety and possible degeneracy in lateral organization in membranes. For our study, we post-process microsecond long all-atom molecular dynamics trajectories for three systems that exhibit fluid phase coexistence: (i) PSM/POPC/Chol (0.47/0.32/0.21), (ii) PSM/DOPC/Chol (0.43/0.38/0.19) and (iii) DPPC/DOPC/Chol (0.37/0.36/0.27). To distinguish the liquid ordered and disordered regions at molecular scales, we calculate the degree of non-affineness of individual lipids in their neighbourhood and track their topological rearrangements. Disconnectivity graph analysis with respect to membrane organization shows that the DPPC/DOPC/Chol and PSM/DOPC/Chol systems exhibit funnel-like energy landscapes as opposed to a highly frustrated energy landscape for the more biomimetic PSM/POPC/Chol system. We use these measurements to develop a continuous lattice Hamiltonian and evolve that using Monte Carlo simulated annealing to explore the possibility of structural degeneracy in membrane organization. Our data show that model membranes with lipid constituents that are biomimetic (PSM/POPC/Chol) have the ability to access a large range of membrane sub-structure space (higher degeneracy) as compared to the other two systems, which form only one kind of substructure even with changing composition. Since the spatiotemporal organization in biological membranes dictates the "molecular encounters" and in turn larger scale biological processes such as molecular transport, trafficking and cellular signalling, we posit that this structural degeneracy could enable access to a larger repository to functionally important molecular organization in systems with physiologically relevant compositions.