**2. Possible ways of controlling cell–cell adhesions**

Currently, there are only a few tools for controlling cell–cell adhesion, which enable the studying of the underlying biology and for bottom-up tissue engineering. Important aspects to consider in the control of cell–cell adhesions are their specificity, their dynamics, and most importantly, their spatiotemporal regulation. The current approaches can be divided into two; the modification of the cell surface with chemically reactive groups and the genetic modification of cells to alter the expression of cell adhesion molecules [37].

In the following sections, we will discuss options of regulating cell–cell adhesions using reactive chemical groups and then consider photoregulation of cell–cell adhesions using light-responsive small molecules and finally optogenetic approaches. Light is especially advantageous as a trigger for cell–cell adhesions since light, as opposed to other stimuli like chemical inputs, temperature, redox etc., can be delivered with superior spatial and temporal control. Using a focused beam of light enables precise subcellular delivery, which can exclude the surrounding area. Secondly, light allows for temporal control as it can be turned on or off instantly making delivery or removal at the desired point instantaneous [38, 39].
