ABSTRACT:

Recent advances in super-resolution microscopy revealed the previously unknown nanoscopic level of organization of endoplasmic reticulum (ER), one of the most vital intracellular organelles. Membrane nanostructures of 10-100nm intrinsic length scales, which include ER tubular matrices, ER sheet nanoholes, internal membranes of ER exit sites (ERES) and ER transport intermediates, were discovered and imaged in considerable detail, but the physical factors determining their unique geometrical features remained unknown. Here we proposed and computationally substantiated a common concept for mechanisms of all four ER nanostructures based on the membrane intrinsic curvature as a primary factor shaping the membrane and ultra-low membrane tensions as modulators of the membrane configurations. We predicted computationally the existence of a discrete series of equilibrium configurations of ER tubular matrices and recovered the one corresponding to the observations and favored by ultra-low tensions.  We modeled the nanohole formation as resulting from a spontaneous collapse of elements of the ER tubular network adjacent to the ER sheet edge and calculated the nanohole dimensions. We proposed the ERES membrane to have a shape of a super-flexible membrane bead-chain, which acquires random-walk configurations unless an ultra-low tension converts it into a straight conformation of a transport intermediate. The adequacy of the proposed concept is supported by a close qualitative and quantitative similarity between the predicted and observed configurations of all four ER nanostructures.

BIO:

Michael M. (Misha) Kozlov is Professor, Department of Physiology and Pharmacology, Sackler Faculty of Medicine at Tel Aviv University and Joseph Klafter Chair in Biophysics.

Research interest: Theoretical Cell Biophysics. Theory of lipid bilayer fusion and fission; Theory of structural transitions in lipid mesaphises; Theory of membrane shaping and remodeling by proteins; Theory of curvature sensing by proteins; Theoretical modeling of cell adhesions; Theoretical modeling of cytoskeletal oganization in cells.