TY - JOUR

T1 - Rhodopsin: The Hydrogen Atom of Membrane Biophysics

AU - Bachler, Zachary T.

AU - Cheng, Evelyn W.

AU - Arruda, Maya N.

AU - Swathi, Melon

AU - Струц, Андрей Владимирович

AU - Бармасов, Александр Викторович

AU - Brown, Michael F.

PY - 2025

Y1 - 2025

N2 - The emergence of lipidomics has established that changes to the lipid composition of membranes can produce physiological changes, but the mechanisms by which these changes occur are not well understood. The classical framework through which lipid-protein interactions are explained is the fluid mosaic model (FMM), which considers lipids as a weakly interacting solvent. However, lipids have repeatedly been shown to influence protein function, both through specific interactions and through nonspecific, collective properties. Here, we discuss the biophysical properties of membranes, such as asymmetry, packing, and elasticity and consider examples where lipid composition is found to influence protein function. Such biophysical properties are subject to homeostasis, with changes in the environment being countered by changes to the lipidome. This energy-intensive process implies evolutionary fitness associated with specific properties, but the exact mechanism by which they affect protein function remains to be elucidated. Determining how membrane properties — tuned by changes to the lipidome — can influence protein function is essential for elucidating the membrane properties underlying homeostasis. Throughout all these studies, rhodopsin has played a pivotal role due to its spectroscopic properties enabling otherwise challenging experiments. We therefore consider rhodopsin as the hydrogen atom of membrane biophysics in recognition of its continued unique significance as a model system. Going forward, we propose that curvature stress is likely as a property to explain the observed strong protein–lipid coupling. Use of the rhodopsin system offers numerous opportunities for understanding the role of membrane curvature adaptation and how it arises from membrane composition and lipid asymmetry in terms of foundational concepts of biophysics.

AB - The emergence of lipidomics has established that changes to the lipid composition of membranes can produce physiological changes, but the mechanisms by which these changes occur are not well understood. The classical framework through which lipid-protein interactions are explained is the fluid mosaic model (FMM), which considers lipids as a weakly interacting solvent. However, lipids have repeatedly been shown to influence protein function, both through specific interactions and through nonspecific, collective properties. Here, we discuss the biophysical properties of membranes, such as asymmetry, packing, and elasticity and consider examples where lipid composition is found to influence protein function. Such biophysical properties are subject to homeostasis, with changes in the environment being countered by changes to the lipidome. This energy-intensive process implies evolutionary fitness associated with specific properties, but the exact mechanism by which they affect protein function remains to be elucidated. Determining how membrane properties — tuned by changes to the lipidome — can influence protein function is essential for elucidating the membrane properties underlying homeostasis. Throughout all these studies, rhodopsin has played a pivotal role due to its spectroscopic properties enabling otherwise challenging experiments. We therefore consider rhodopsin as the hydrogen atom of membrane biophysics in recognition of its continued unique significance as a model system. Going forward, we propose that curvature stress is likely as a property to explain the observed strong protein–lipid coupling. Use of the rhodopsin system offers numerous opportunities for understanding the role of membrane curvature adaptation and how it arises from membrane composition and lipid asymmetry in terms of foundational concepts of biophysics.

KW - родопсин

KW - мембраны

M3 - Article

VL - 124

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

ER -