Biology subjects

Stachowiak, J.

Publications and source records attributed to Stachowiak, J..

21 records · Page 2Linked to original sources

bioRxiv2021

A continuum membrane model predicts curvature sensing by helix insertion

Protein domains, such as ENTH (Epsin N-terminal homology) and BAR (bin/amphiphysin/rvs), contain amphipathic helices that drive preferential binding to curved membranes. However, predicting how the physical parameters of these domains control this curvature sensing behavior is challenging due to the local membrane deformations generated by the nanoscopic helix on the surface of a large sphere. To overcome this challenge, we here use a deformable continuum model that accounts for the physical properties of the membrane and the helix insertion to predict curvature sensing behavior and is in good agreement with existing experimental data. Specifically, we show that the insertion can be modeled as a local change to the membranes spontaneous curvature,[Formula]. Using physically reasonable ranges of the membrane bending modulus [kcy], and a [Formula] of [~]0.2-0.3 nm-1, this approach provides excellent agreement with the energetics extracted from experiment. For small vesicles with high curvature, the insertion lowers the membrane energy by relieving strain on a membrane that is far from its preferred curvature of zero. For larger vesicles with low curvature, however, the insertion has the inverse effect, de-stabilizing the membrane by introducing more strain. The membrane energy cannot be directly predicted analytically, due to shape changes from surface relaxation around the anisotropic insertion. We formulate here an empirical expression that captures numerically calculated membrane energies as a function of both basic membrane properties (bending modulus [kcy] and radius R) as well as stresses applied by the inserted helix ([Formula] and area Ains). We show that the shape relaxation energy has a similar magnitude to the insertion energy, with a strong nonlinear dependence on [Formula]. We therefore predict how these physical parameters will alter the energetics of helix binding to curved vesicles, which is an essential step in understanding their localization dynamics during membrane remodeling processes.

biophysics↗

bioRxiv2018

BAR scaffolds drive membrane fission by crowding disordered domains

Cylindrical protein scaffolds are thought to stabilize membrane tubules, preventing membrane fission. In contrast, Snead et al. find that when scaffold proteins assemble, bulky disordered domains within them become acutely concentrated, generating steric pressure that destabilizes tubules, driving fission.\n\nAbstractCellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysinrvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of BAR domains in isolation, the current paradigm is that they polymerize into cylindrical scaffolds that stabilize lipid tubules, preventing membrane fission. But in nature BAR domains are often part of multi-domain proteins that contain large intrinsically-disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain-containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data challenge the idea that cellular membranes adopt the curvature of BAR scaffolds, suggesting instead that the ability to concentrate disordered domains is the key requirement for membrane remodeling and fission by BAR domain-containing proteins.

biophysics↗

bioRxiv2017

The role of traction in membrane curvature generation

Curvature of biological membranes can be generated by a variety of molecular mechanisms including protein scaffolding, compositional heterogeneity, and cytoskeletal forces. These mechanisms have the net effect of generating tractions (force per unit length) on the bilayer that are translated into distinct shapes of the membrane. Here, we demonstrate how the local shape of the membrane can be used to infer the traction acting locally on the membrane. We show that buds and tubes, two common membrane deformations studied in trafficking processes, have different traction distributions along the membrane and that these tractions are specific to the molecular mechanism used to generate these shapes. Furthermore, we show that the magnitude of an axial force applied to the membrane as well as that of an effective line tension can be calculated from these tractions. Finally, we consider the sensitivity of these quantities with respect to uncertainties in material properties and follow with a discussion on sources of uncertainty in membrane shape.

biophysics↗