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.