1.
Optogenetic engineering of lipid droplet spatial organization for tumor suppression.
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Bai, Q
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Shao, X
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Xia, Q
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Yang, S
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Gao, Y
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Sun, K
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Li, J
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Wang, X
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Tian, Z
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Chen, X
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Zhao, J
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Diao, J
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Chen, Q
Abstract:
In cancer cells, lipid droplets (LDs) establish extensive membrane contact sites (MCSs) with mitochondria to facilitate fatty acid transfer and sustain energy production, thus enabling cancer cell survival, in nutrient-deprived tumor microenvironments. However, effective strategies to disrupt these LD-mitochondria interactions remain unavailable. We engineered an optogenetic system to control LD intracellular organization through clustering. Upon blue light stimulation, the system induces LDs to undergo spatial reorganization and form clusters, thereby restricting LD accessibility by reducing the available surface area for mitochondrial interaction. Consequently, this clustering significantly diminishes the number of LD-mitochondria MCSs, suppresses fatty acid transport from LDs to mitochondria during starvation, and ultimately leads to cancer cell death in vitro and tumor growth inhibition in vivo. Collectively, our results demonstrate that optogenetically controlled LD clustering offers a novel approach to impede tumor progression by blocking nutrient flow from LDs to mitochondria.
2.
Orthogonal Light-Dependent Membrane Adhesion Induces Social Self-Sorting and Member-Specific DNA Communication in Synthetic Cell Communities.
Abstract:
Developing orthogonal chemical communication pathways in diverse synthetic cell communities is a considerable challenge due to the increased crosstalk and interference associated with large numbers of different types of sender-receiver pairs. Herein, the authors control which sender-receiver pairs communicate in a three-membered community of synthetic cells through red and blue light illumination. Semipermeable protein-polymer-based synthetic cells (proteinosomes) with complementary membrane-attached protein adhesion communicate through single-stranded DNA oligomers and synergistically process biochemical information within a community consisting of one sender and two different receiver populations. Different pairs of red and blue light-responsive protein-protein interactions act as membrane adhesion mediators between the sender and receivers such that they self-assemble and socially self-sort into different multicellular structures under red and blue light. Consequently, distinct sender-receiver pairs come into the signaling range depending on the light illumination and are able to communicate specifically without activation of the other receiver population. Overall, this work shows how photoswitchable membrane adhesion gives rise to different self-sorting protocell patterns that mediate member-specific DNA-based communication in ternary populations of synthetic cells and provides a step towards the design of orthogonal chemical communication networks in diverse communities of synthetic cells.
