Membrane Tubulation by Cytoskeletal System: From Physical Principles to Cellular Mechanisms and In Vitro...

Membrane tubes are thin, cylindrical lipid bilayer structures that are ubiquitous in cells and participate in a wide range of biological processes, from plasma membrane protrusions that interact with the external environment to elongated tubules of intracellular organelles involved in trafficking pathways. While membrane tubes represent a thermodynamically accessible mode of membrane deformation owing to the inherent fluidity and bending susceptibility of lipid bilayers, the formation and maintenance of most cellular membrane tubes are actively regulated by cytoskeletal proteins. Cytoskeleton-driven tubulation can be classified into two mechanically distinct mechanisms: filament polymerization within the tube lumen that pushes the membrane outward, and pulling forces exerted on the outer tube surface either through polymerization dynamics or by motor proteins walking along cytoskeletal tracks. In this review, for each class of cytoskeleton-driven membrane tubes, we introduce the corresponding cellular structures, outline the key formation principles, and discuss the mechanistic insights and theoretical models derived from in vitro reconstitution studies. As both membrane tubes and cytoskeletal filaments are one-dimensional elastic structures amenable to rigorous physical formulation, they represent an exemplary case in which in vivo observations and in vitro approaches have advanced in a complementary and mutually informative manner.