Abstract
Directed transport of proteins and other molecules in a crowded living cell is often carried out by diffusion at short distances and by motor-driven cargo transport over long distances. Here we demonstrate, by both experiments and theory, that anchored proteins inside the cell can generate a spatially varying and temporally stable potential (free-energy) landscape for intracellular or membrane transport in the mesoscale. By using a micropatterned substrate, we introduce a periodic array of anchored integrins on the basal membrane of cultured Xenopus muscle cells. This patterned array of anchored integrins imposes a periodic potential $U(x)$ to the lateral motion of nicotinic acetylcholine receptors (AChRs) on the cell membrane. From a thorough analysis of a large volume of AChR trajectories obtained over a wide range of sampling conditions and long durations from 385 cells, we find the trapping potential $U(x)$ and its effects on the drift velocity ${V}_{x}(x)$ and diffusion coefficient ${D}_{x}(x)$ of AChRs. Our findings suggest that anchored proteins may play an essential role in generating an effective potential landscape to guide molecular motion in the mesoscale ranging from protein trapping and directed motion to enhanced protein-protein interactions over a long range.
Highlights
A living cell is a densely packed compartment filled with individual proteins, lipids, and sugars in the cell cytoplasm, as well as the filamentous networks permeating the cell [1]
This gives rise to an entropy-driven potential field U (x) n(x)kBT for mobile proteins, pushing them to move from a high concentration region of anchored proteins to a low concentration region
Higher energy barriers can be obtained if the effects of the size and concentration of the anchored proteins and their interactions with mobile proteins are included
Summary
A living cell is a densely packed compartment filled with individual proteins, lipids, and sugars in the cell cytoplasm, as well as the filamentous networks permeating the cell [1]. In the study of membrane diffusion of eukaryotic cells, one found that about half of the transmembrane proteins, corresponding to 10–20 % of total membrane area, are bound to the underlying cortical actin network and, are effectively immobile on timescales of minutes to hours [16] These anchored proteins were assumed to be random obstacles in the membrane and hinder the motion of other mobile proteins [17,18,19,20,21,22,23]. In this paper we demonstrate, by both experiments and theory, that a nonuniform concentration field n(r) of anchored proteins can generate a spatially varying and temporally stable potential (free-energy) landscape U (r) to other (nonmotor) mobile proteins in the region This entropy-driven potential field offers a novel way for directed molecular transport in the mesoscale (20 nm–1 μm), which complements the conventional methods of directed molecular transport by diffusion at short distances and motor-driven cargo transport over long distances.
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