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Veprek, N. A.

Publications and source records attributed to Veprek, N. A..

2 recordsLinked to original sources
bioRxiv2022

Next Generation Opto-Jasplakinolides Enable Local Remodeling of Actin Networks

The natural product jasplakinolide is a widely used tool compound to stabilize F-actin and influence actin dynamics. We have previously introduced photoswitchable jasplakinolides (optojasps) that are activated with violet light and deactivated with blue light. Based on insights from cryo-electron microscopy and structure-activity relationship (SAR) studies, we now developed a new generation of functionally superior optojasps that are better suited for biological investigations. These compounds are procured through chemical total synthesis and feature rationally designed red-shifted azobenzene photoswitches. Our new optojasps can be activated with longer wavelengths in the visible range (e.g. 440-477 nm) and rapidly return to their inactive state through thermal relaxation. This has enabled the reversible control of F-actin dynamics, as shown through live-cell imaging and cell migration, as well as cell proliferation assays. Brief sub-cellular activation with blue-green light resulted in highly localized F-actin clusters that gradually dissolved in the dark. Our light-responsive tools can be useful in diverse fields to study actin dynamics with outstanding spatiotemporal precision. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/480923v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1883e3corg.highwire.dtl.DTLVardef@1ae0c4borg.highwire.dtl.DTLVardef@1a92f8forg.highwire.dtl.DTLVardef@718d87_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗
bioRxiv2022

Optical Control of Membrane Fluidity Modulates Protein Secretion

The lipid composition of cellular membranes is dynamic and undergoes remodelling affecting biophysical properties, such as membrane fluidity, which are critical to biological function. Here, we introduce an optical approach to manipulate membrane fluidity based on exogenous synthetic fatty acid with an azobenzene photoswitch, termed FAAzo4. Cells rapidly incorporate FAAzo4 into phosphatidylcholine (PC), the major phospholipid in mammalian cells, in a concentration- and cell type-dependent manner. This generates photoswitchable PC analogs (AzoPC), which are predominantly located in the endoplasmic reticulum (ER). Irradiation causes a rapid photoisomerization that increases membrane fluidity with high spatiotemporal precision. We use these PhotoCells to study the impact of membrane mechanics on protein export from the ER and demonstrate that this two-step process has distinct membrane fluidity requirements. Our approach represents an unprecedented way of manipulating membrane fluidity in cellulo and opens novel avenues to probe roles of fluidity in a wide variety of biological processes.

cell biology↗