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Rojas Molina, R. V.

Publications and source records attributed to Rojas Molina, R. V..

2 recordsLinked to original sources

Protein diffusion on membrane domes, tubes and pearling structures

Diffusion is a fundamental mechanism for protein distribution in cell membranes. These membranes often exhibit complex shapes, which range from shallow domes to elongated tubular or pearl-like structures. Shape complexity of the membrane influences the diffusive spreading of proteins and molecules. Despite the importance membrane geometry plays in these diffusive processes, it is challenging to establish the dependence between diffusion and membrane morphology. We solve the diffusion equation numerically on various curved shapes representative for experimentally observed membrane shapes. Our results show that membrane necks become diffusion barriers. We determine the diffusive half time, i.e., the time that is required to reduce the amount of proteins in the budded region by one half and find a quadratic relation between the diffusive half time and the averaged mean curvature of the membrane shape. Our findings thus help to estimate the characteristic diffusive time scale based on the simple measure for membrane morphology. Significance statementDiffusion is an integral process for distributing proteins throughout biological membranes. These membranes can have complex shapes and structures, often featuring elongated shapes such as tubes and like a necklace of pearls. The diffusion process on these shapes is significantly different from the well studied planar substrate. We use numerical simulations to understand how the characteristic diffusion time is a function of membrane shape, where we find the diffusion of proteins on strongly curved shapes is significantly slower than on planar membranes. Our results provide a simple relationship to estimate the characteristic diffusion time of proteins on membranes based on its mean and Gaussian curvature.

biophysics↗

Protein Crowding mediates Passive Membrane Remodeling in ESCRT-induced Formation of Intraluminal Vesicles

As part of the lysosomal degradation pathway, the endosomal sorting complexes required for transport (ESCRT-0-III/VPS4) sequester receptors at the endosome and simultaneously deform the membrane to generate intraluminal vesicles (ILVs). Whereas ESCRT-III/VPS4 have an established function in ILV formation, the role of upstream ESCRTs (0-II) in membrane shape remodeling is not understood. Combining experimental measurements and electron microscopy analysis of ESCRT-III depleted cells with a mathematical model, we show that upstream ESCRT-induced alteration of the Gaussian bending rigidity and their crowding on the membrane induces membrane deformation and facilitates ILV formation: upstream ESCRT-driven budding does not require ATP consumption as only a small energy barrier needs to be overcome. Our model predicts that ESCRTs do not become part of the ILV, but localize with a high density at the membrane neck, where the steep decline in the Gaussian curvature likely triggers ESCRT-III/VPS4 assembly to enable neck constriction and scission.Significance Statement Intraluminal vesicle (ILV) formation plays a crucial role in the attenuation of growth factor receptor signaling, which is mediated by the endosomal sorting complex required for transport (ESCRT-0-III/VPS4). The general dogma has been that the upstream ESCRTs (0-II) sequester the receptors at the surface of endosomes and the downstream ESCRTs (III/VPS4) remodel the endosome membrane leading to the abscission and formation of receptor-containing ILVs. We now show that the upstream ESCRTs not only sequester cargo, but in addition play an essential role for the initiation of membrane shape remodeling in ILV budding. Through a combination of mathematical modeling and experimental measurements we show that upstream ESCRTs facilitate ILV budding by crowding with a high density in the membrane neck region.Competing Interest StatementThe authors have declared no competing interest.View Full Text

biophysics↗