What is it about?

Plasma membrane heterogeneity is a key biophysical regulatory principle of membrane protein dynamics. In this work, we developed a high-spatial resolved DNA-origami-based nanoheater system to manipulate the local lipid environmental temperature under near-infrared laser illumination. This high spatial-resolved, raft/non-raft domain-targeted nanodevices not only alters local membrane fluidity but also interferes with membrane phase separation through highly specified manipulation

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Why is it important?

Although the lipid raft hypothesis has gained great success, a direct link between membrane heterogeneity and cell biological processes remains poorly understood. This is, at least in part, due to the shortage of high spatial-resolved molecule tools to interfere with the membrane heterogeneity and find its correlation to cell functions. We provided, for the first time, a high spatial-solved, remote-controlled, domain-targeted, and reversible molecule tool to alter membrane heterogeneity through physical property change. This molecule tool enables to control signal pathway change, possibly through regulating dynamic assemblies and function of membrane-bound receptors, thereby featuring the capability to build a direct, unexplored correlation between membrane heterogeneity and cell function, which holds great potential in therapy.

Perspectives

The fundamental of these nanoheater systems is to regulate lipid heterogeneity in the plasma membrane, which is not only a key regulator for cell migration but also varies in signal pathways. Since different types of cells have different dominant signal pathways, certain outcomes other than cell migration are out of the scope of this research. However, this nanoheater system might have a broader spectrum of applications that we are currently unaware of. Moreover, considering the heating is a result of photothermal treatment, besides the domain-dependent spatial resolution, it also possesses a higher temporal resolution. Therefore, a remote regulation of cellular behaviors at different cell cycles is also anticipated. The ability of domain-dependent regulating cell membrane heterogeneity enables us to explore the underestimated biological function of lipid rafts, providing a possibility to set a direct correlation of physical (size, lifetime, and so on) and compositional features of lipid raft with physiological functions (differentiation, programmed death, and metabolism) on both cells and potentially tissue of cells.

Di Li
East China Normal University

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This page is a summary of: High spatial-resolved heat manipulating membrane heterogeneity alters cellular migration and signaling, Proceedings of the National Academy of Sciences, November 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2312603120.
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