High spatial-resolved heat manipulating membrane heterogeneity alters cellular migration and signaling

Author:

Chen Xiaoqing1,Yang Qianyun1,Kong Wenyan2,Ge Yifan2ORCID,He Jie1ORCID,Yan An1,Li Di1ORCID

Affiliation:

1. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

2. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China

Abstract

Plasma membrane heterogeneity is a key biophysical regulatory principle of membrane protein dynamics, which further influences downstream signal transduction. Although extensive biophysical and cell biology studies have proven membrane heterogeneity is essential to cell fate, the direct link between membrane heterogeneity regulation to cellular function remains unclear. Heterogeneous structures on plasma membranes, such as lipid rafts, are transiently assembled, thus hard to study via regular techniques. Indeed, it is nearly impossible to perturb membrane heterogeneity without changing plasma membrane compositions. In this study, we developed a high-spatial resolved DNA-origami-based nanoheater system with specific lipid heterogeneity targeting to manipulate the local lipid environmental temperature under near-infrared (NIR) laser illumination. Our results showed that the targeted heating of the local lipid environment influences the membrane thermodynamic properties, which further triggers an integrin-associated cell migration change. Therefore, the nanoheater system was further applied as an optimized therapeutic agent for wound healing. Our strategy provides a powerful tool to dynamically manipulate membrane heterogeneity and has the potential to explore cellular function through changes in plasma membrane biophysical properties.

Funder

MOST | National Natural Science Foundation of China

NJU | State Key Laboratory of Analytical Chemistry for Life Science

CAS | CIAC | State Key Laboratory of Electroanalytical Chemistry

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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