Curated Optogenetic Publication Database

Abstract: The regulation of cell–cell adhesions in space and time plays a crucial role in cell biology, especially in the coordination of multicellular behavior. Therefore, tools that allow for the modulation of cell–cell interactions with high precision are of great interest to a better understanding of their roles and building tissue‐like structures. Herein, the green light‐responsive protein CarH is expressed at the plasma membrane of cells as an artificial cell adhesion receptor, so that upon addition of its cofactor vitamin B12 specific cell–cell interactions form and lead to cell clustering in a concentration‐dependent manner. Upon green light illumination, the CarH based cell–cell interactions disassemble and allow for their reversion with high spatiotemporal control. Moreover, these artificial cell–cell interactions impact cell migration, as observed in a wound‐healing assay. When the cells interact with each other in the presence of vitamin B12 in the dark, the cells form on a solid front and migrate collectively; however, under green light illumination, individual cells migrate randomly out of the monolayer. Overall, the possibility of precisely controlling cell–cell interactions and regulating multicellular behavior is a potential pathway to gaining more insight into cell–cell interactions in biological processes.

Abstract: The self-assembly of different cell types into multicellular structures and their organization into spatiotemporally controlled patterns are both challenging and extremely powerful to understand how cells function within tissues and for bottom-up tissue engineering. Here, we not only independently control the self-assembly of two cell types into multicellular architectures with blue and red light, but also achieve their self-sorting into distinct assemblies. This required developing two cell types that form selective and homophilic cell-cell interactions either under blue or red light using photoswitchable proteins as artificial adhesion molecules. The interactions were individually triggerable with different colors of light, reversible in the dark, and provide noninvasive and temporal control over the cell-cell adhesions. In mixtures of the two cells, each cell type self-assembled independently upon orthogonal photoactivation, and cells sorted out into separate assemblies based on specific self-recognition. These self-sorted multicellular architectures provide us with a powerful tool for producing tissue-like structures from multiple cell types and investigate principles that govern them.

Abstract: Building tissue from cells as the basic building block based on principles of self-assembly is a challenging and promising approach. Understanding how far principles of self-assembly and self-sorting known for colloidal particles apply to cells remains unanswered. In this study, we demonstrate that not just controlling the cell-cell interactions but also their dynamics is a crucial factor that determines the formed multicellular structure, using photoswitchable interactions between cells that are activated with blue light and reverse in the dark. Tuning dynamics of the cell-cell interactions by pulsed light activation, results in multicellular architectures with different sizes and shapes. When the interactions between cells are dynamic compact and round multicellular clusters under thermodynamic control form, while otherwise branched and lose aggregates under kinetic control assemble. These structures parallel what is known for colloidal assemblies under reaction and diffusion limited cluster aggregation, respectively. Similarly, dynamic interactions between cells are essential for cells to self-sort into distinct groups. Using four different cell types, which expressed two orthogonal cell-cell interaction pairs, the cells sorted into two separate assemblies. Bringing concepts of colloidal self-assembly to bottom-up tissue engineering provides a new theoretical framework and will help in the design of more predictable tissue-like structures.

Abstract: Controlling cell–cell interactions is central for understanding key cellular processes and bottom-up tissue assembly from single cells. The challenge is to control cell–cell interactions dynamically and reversibly with high spati- otemporal precision noninvasively and sustainably. In this study, cell–cell interactions are controlled with visible light using an optogenetic approach by expressing the blue light switchable proteins CRY2 or CIBN on the surfaces of cells. CRY2 and CIBN expressing cells form specific heterophilic interactions under blue light providing precise control in space and time. Further, these interactions are reversible in the dark and can be repeatedly and dynamically switched on and off. Unlike previous approaches, these genetically encoded proteins allow for long-term expression of the interaction domains and respond to nontoxic low intensity blue light. In addition, these interactions are suitable to assemble cells into 3D multicellular architectures. Overall, this approach captures the dynamic and reversible nature of cell–cell interactions and controls them noninvasively and sustainably both in space and time. This provides a new way of studying cell–cell interactions and assembling cellular building blocks into tissues with unmatched flexibility.