Abstract
Macromolecular crowding is the usual condition of cells. The implications of the crowded cellular environment for protein stability and folding, protein-protein interactions, and intracellular transport drive a growing interest in quantifying the effects of crowding. While the properties of crowded solutions have been extensively studied, less attention has been paid to the interaction of crowders with the cellular boundaries, i.e., membranes. However, membranes are key components of cells and most subcellular organelles, playing a central role in regulating protein channel and receptor functions by recruiting and binding charged and neutral solutes. While membrane interactions with charged solutes are dominated by electrostatic forces, here we show that significant charge-induced forces also exist between membranes and neutral solutes. Using neutron reflectometry measurements and molecular dynamics simulations of poly(ethylene glycol) (PEG) polymers of different molecular weights near charged and neutral membranes, we demonstrate the roles of surface dielectrophoresis and counterion pressure in repelling PEG from charged membrane surfaces. The resulting depletion zone is expected to have consequences for drug design and delivery, the activity of proteins near membrane surfaces, and the transport of small molecules along the membrane surface.
| Original language | English |
|---|---|
| Pages (from-to) | 2701-2710 |
| Number of pages | 10 |
| Journal | Journal of the American Chemical Society |
| Volume | 146 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 31 2024 |
Funding
The authors wish to thank F. Heinrich and K. Rubinson for helpful discussions. Access to CANDOR was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under Agreement No. DMR-2010792. A portion of this research used resources at the Spallation Neutron Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated by the Oak Ridge National Laboratory. Some of the neutron reflectometry measurements were carried out on the Liquids Reflectometer at the SNS, which is sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, DOE. ORNL is managed by UT-Battelle LLC for DOE under Contract DE-AC05-00OR22725. M.A-A. and V.M.A. acknowledge funding by the Spanish MCIN/AEI/10.13039/501100011033/FEDER, UE (project PID2022-142795 NB-I00) and Universitat Jaume I (project UJI-B2022-42).