4.5 Article

Observed steric crowding at modest coverage requires a particular membrane-binding scheme or a complementary mechanism

Journal

BIOPHYSICAL JOURNAL
Volume 121, Issue 3, Pages 430-438

Publisher

CELL PRESS
DOI: 10.1016/j.bpj.2021.12.036

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Funding

  1. Eunice Kennedy Shriver National Institute of Child Health and the Human Development of the National Institutes of Health

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Membrane shape transitions, such as fusion and fission, are crucial in biological processes. Understanding the mechanisms of curvature generation, including the effect of steric pressure from crowded proteins, is essential. The previously understood model is split into two parts: the reduction in steric pressure due to reduced collisions between proteins and the increased area available to individual proteins. The revised theory suggests that a purely entropic crowding mechanism cannot explain observations of reshaping at lower surface coverage, implying the presence of additional mechanisms.
Membrane shape transitions, including fusion and fission, play an important role in many biological processes. It is therefore essential to understand mechanisms of curvature generation,the mathematical quantification of membrane shape. Among the different mechanisms is the effect of steric pressure between proteins crowded on a surface. At a higher curvature, there is more space for the crowders and less steric pressure. Currently, the physical model of curvature induction by crowding views the proteins as being bound to the surface as a whole rather than to the underlying lipids. Here, we split the previously understood model into two pieces: first, the reduction in steric pressure due to reduced collisions between proteins, and second, the increased area available to the protein that is independent of other crowders. The cases are distinguished by how the crow der is attached to the membrane. When a protein is attached to a specific lipid, as is the case in a typical crowding experiment, one should not model its lateral entropy; this has already been accounted for by the underlying lipid. The Carnahan-Starling pressure includes this lateral entropy. The revised theory predicts that a purely entropic crowding mechanism is inconsistent with observations of reshaping at the lower range of surface coverage, suggesting that an additional mechanism is at play.

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