Fig. 6: Optical control of membrane protein function and secretion via photolipid isomerization.

a Current traces of MscL activation. MscL were reconstituted in binary lipid membranes of 20% azo-PC and 80% DPhPC. After cis-to-trans switching with blue light of 455 nm and a delay time of 5 s (green bar), spontaneous openings of the channel were observed (red arrow). Reprinted (adapted) with permission from Front. Mol. Biosci., 9, 2022⁸³. Copyright © 2022 Crea, Vorkas, Redlich, Cruz, Shi, Trauner, Lange, Schlesinger and Heberle. b Quantification of the increase of the mean relative open probability of MscL upon trans (dotted bars) to cis (gray bars) isomerization of 4-Azo-5P: 30-40 s and 130–140 s of illumination at 365 nm and subsequent 50 s illumination at 436 nm (190-200 s). The open probability of the MscL channel from 0 to 10 s was indexed at 1. Error bars indicate the standard error of the mean. Reprinted (adapted) with permission from Langmuir 2004, 20, 17, 6985-6987⁷². Copyright 2004 American Chemical Society. c Selective activation of mTOR signaling in the presence of photolipids (Azo- and dAzo phosphatidic acids). Left: Diagram illustrating mTOR signaling through activation of the key downstream target p70-S6 kinase (mTORC1). The activation of mTORC1 was evaluated by measuring levels of S6K phosphorylated at Thr389 (p-S6K) using Western blot analysis. Right: Quantification of immunofluorescence analysis, showing the average p-S6 intensity per Serum-starved NIH 3T3 cell. Black horizontal bars represent the mean (n = 10−14), with vertical error bars indicating standard deviation. Statistical significance was determined using one-way ANOVA, followed by Tukey’s HSD test. Cells treated with cis-dAzoPA exhibited a substantial increase in p-S6 levels. Notably, these effects were specific to dAzoPA and not AzoPA, indicating a high degree of acyl chain selectivity in PA-induced mTOR signaling activation. Reprinted (adapted) with permission from CS Cent. Sci. 2021, 7, 7, 1205–1215⁶⁸. Copyright 2021 American Chemical Society under license CC-BY-NC-ND 4.0. d Optical control of Hippo signaling in NIH 3T3 cells. Left: Schematic representation of the optical control of Hippo deactivation induced by phosphatidic acid (PA). When Hippo signaling is active, LATS1/2 kinases phosphorylate the transcription factor YAP, preventing its translocation to the nucleus. PA can bind to both LATS1/2 and the upstream factor NF2, inhibiting Hippo signaling. Right: Quantification of nuclear YAP levels. The plots show the mean nuclear YAP intensity per cell. Black horizontal bars represent the mean (n = 342 (upper plot) and 465 (lower plot)), with vertical error bars indicating standard deviation. Statistical significance was again determined using one-way ANOVA followed by Tukey’s HSD test. Notably, both cis-AzoPA and cis-dAzoPA, but not their trans isomers, induced nuclear translocation of YAP. Reprinted (adapted) with permission from ACS Cent. Sci. 2021, 7, 7, 1205–1215⁶⁸. Copyright 2021 American Chemical Society under license CC-BY-NC-ND 4.0.