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Atomistic molecular dynamics simulations of concentrated protein solutions in the presence of a phospholipid bilayer are presented to gain insights into the dynamics and interactions at the cytosol–membrane interface. The main finding is that proteins that are not known to specifically interact with membranes are preferentially excluded from the membrane, leaving a depletion zone near the membrane surface. As a consequence, effective protein concentrations increase, leading to increased protein contacts and clustering, whereas protein diffusion becomes faster near the membrane for proteins that do occasionally enter the depletion zone. Since protein–membrane contacts are infrequent and short-lived in this study, the structure of the lipid bilayer remains largely unaffected by the crowded protein solution, but when proteins do contact lipid head groups, small but statistically significant local membrane curvature is induced, on average.
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Proteins Adsorbing onto Surface-Modified Nanoparticles: Effect of Surface Curvature, pH, and the Interplay of Polymers and Proteins Acid–Base Equilibrium
Protein adsorption onto nanomaterials is a process of vital significance and it is commonly controlled by functionalizing their surface with polymers. The efficiency of this strategy depends on the design parameters of the nanoconstruct. Although significant amount of work has been carried out on planar surfaces modified with different types of polymers, studies investigating the role of surface curvature are not as abundant. Here, we present a comprehensive and systematic study of the protein adsorption process, analyzing the effect of curvature and morphology, the grafting of polymer mixtures, the type of monomer (neutral, acidic, basic), the proteins in solution, and the conditions of the solution. The theoretical approach we employed is based on a molecular theory that allows to explicitly consider the acid–base reactions of the amino acids in the proteins and the monomers on the surface. The calculations showed that surface curvature modulates the molecular organization in space, but key variables are the bulk pH and salt concentration (in the millimolar range). When grafting the NP with acidic or basic polymers, the surface coating could disfavor or promote adsorption, depending on the solution’s conditions. When NPs are in contact with protein mixtures in solution, a nontrivial competitive adsorption process is observed. The calculations reflect the balance between molecular organization and chemical state of polymers and proteins, and how it is modulated by the curvature of the underlying surface.
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- Award ID(s):
- 1833214
- PAR ID:
- 10369153
- Date Published:
- Journal Name:
- Polymers
- Volume:
- 14
- Issue:
- 4
- ISSN:
- 2073-4360
- Page Range / eLocation ID:
- 739
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/polym14040739
