Nikhil Walani | University of Houston (original) (raw)
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Papers by Nikhil Walani
Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membra... more Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles; it plays an integral role in nutrient import, signal transduction, neurotransmission, and cellular entry of pathogens and drug-carrying nanoparticles. Because CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high-tension conditions, actin dynamics is required to carry
out CME successfully. In this study, we build on these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins—namely, actin and BAR proteins—in driving vesicle formation in high membrane tension environment. Our study reveals an actin force-induced “snapthrough instability” that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a rather counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin–BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells
Symmetry restrictions due to fluidity require the strain energy in the Helfrich theory of lipid m... more Symmetry restrictions due to fluidity require the strain energy in the Helfrich theory of lipid membranes to be locally isotropic in nature. Although this framework is suitable for modeling the interaction of membranes with proteins that generate spherical curvature such as clathrin, there are other important membrane-bending proteins such as BIN-amphiphysin-Rvs proteins that form a cylindrical coat with different curvatures in the longitudinal and the circumferential directions. In this work, we present a detailed mathematical treatment of the theory of lipid membranes incorporating anisotropic spontaneous curvatures. We derive the associated Euler-Lagrange equations and the edge conditions in a generalized setting that allows spatial heterogeneities in the properties of the membrane-protein system. We employ this theory to model the constriction of a membrane tubule by a cylindrical scaffold. In particular, we highlight the role of the equilibrium equation in the tangential plane in regulating the spatial variation of the surface tension field.
Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membra... more Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles; it plays an integral role in nutrient import, signal transduction, neurotransmission, and cellular entry of pathogens and drug-carrying nanoparticles. Because CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high-tension conditions, actin dynamics is required to carry
out CME successfully. In this study, we build on these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins—namely, actin and BAR proteins—in driving vesicle formation in high membrane tension environment. Our study reveals an actin force-induced “snapthrough instability” that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a rather counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin–BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells
Symmetry restrictions due to fluidity require the strain energy in the Helfrich theory of lipid m... more Symmetry restrictions due to fluidity require the strain energy in the Helfrich theory of lipid membranes to be locally isotropic in nature. Although this framework is suitable for modeling the interaction of membranes with proteins that generate spherical curvature such as clathrin, there are other important membrane-bending proteins such as BIN-amphiphysin-Rvs proteins that form a cylindrical coat with different curvatures in the longitudinal and the circumferential directions. In this work, we present a detailed mathematical treatment of the theory of lipid membranes incorporating anisotropic spontaneous curvatures. We derive the associated Euler-Lagrange equations and the edge conditions in a generalized setting that allows spatial heterogeneities in the properties of the membrane-protein system. We employ this theory to model the constriction of a membrane tubule by a cylindrical scaffold. In particular, we highlight the role of the equilibrium equation in the tangential plane in regulating the spatial variation of the surface tension field.