Analysis and regulation of amoeboid-like cell motility using synthetic Ca2+-sensitive proteins

Several recent reports have demonstrated how engineered proteins can control cell motility, an important functional module for ultimately programming cells as therapeutics. We have reported two engineered proteins that regulate the blebbing cell morphology using chimeras of RhoA, a protein that regulates cytoskeletal tension. Here, we show that engineered switching of blebbing can be used to regulate cell motility. First, the analysis of morphology and motility characteristics showed that blebbing cells wobbled, or shifted, faster and less linearly than cells with a wild type morphology. Second, activating engineered protein switches that regulate cell morphology led to predictable changes in motility characteristics. Last, exogenous stimuli such as blue light, acetylcholine and VEGF-A were used to show that groups of proteins could cooperatively increase cell motility in vitro. This work demonstrates that control of RhoA can program the motility patterns of living cells and has implications in studying the relationship between cell morphology and motility.