Topographic Modulation of Acetylcholine Receptors Diffusion Dynamics on Live Cell Membrane

Abstract

In a recent single-molecule tracking experiment [1], the acetylcholine receptors (AChRs) on muscle cell membranes were found to display non-Gaussian statistics due to dynamic heterogeneity resulting from the complex cellular environment of the AChRs. In this study, we vary the cellular environment of AChRs by using the microgroove patterning techniques to control the spatial distribution of adhesion complexes on the basal membrane of live cells and study its effect on the diffusion dynamics of AChRs. Cultured Xenopus muscle cells are found to align along the microgroove patterns with their adhesion complexes, such as β1-integrins, predominantly anchored on the ridge region of the microgrooves, forming a stripe-like pattern. Interestingly, we find the movement of AChRs is largely restricted within the microgroove-aligned integrin stripes. Detailed statistical analysis of the AChR trajectories reveals that the AChRs are slowed down by the patterned integrins, and immobilization and clustering of the AChRs are correlated with the spatial distribution of integrins. The experiment demonstrates that the spatial distribution of integrins plays a crucial role in modulating the diffusion dynamics of AChRs. ∗The work was supported by the Research Grants Council of Hong Kong SAR. [1] W. He, H. Song, Y. Su, L. Geng, B. J. Ackerson, H. B. Peng, and P. Tong, Nature Communications, 7:11701 (2016).