With the ultimate aim to construct a living cell, bottom-up synthetic biology strives to reconstitute cellular phenomena in vitro - disentangled from the complex environment of a cell. Recent work towards this ambitious goal has provided new insights into the mechanisms governing life. With the fast-growing library of functional modules for synthetic cells, their classification and integration become increasingly important. We discuss strategies to reverse-engineer and recombine functional parts for synthetic eukaryotes, mimicking the characteristics of nature's own prototype. Particularly, we focus on large outer compartments, complex endomembrane systems with organelles, and versatile cytoskeletons as hallmarks of eukaryotic life. Moreover, we identify microfluidics and DNA nanotechnology as two technologies that can integrate these functional modules into sophisticated multifunctional synthetic cells.

Regulating the emergence of leaders is a central aspect of collective cell migration, but the underlying mechanisms remain ambiguous. Here we show that the selective emergence of leader cells at the epithelial wound-margin depends on the dynamics of the follower cells and is spatially limited by the length-scale of collective force transduction. Owing to the dynamic heterogeneity of the monolayer, cells behind the prospective leaders manifest locally increased traction and monolayer stresses much before these leaders display any phenotypic traits. Followers, in turn, pull on the future leaders to elect them to their fate. Once formed, the territory of a leader can extend only to the length up-to which forces are correlated, which is similar to the length up-to which leader cells can transmit forces. These findings provide mechanobiological insight into the hierarchy in cell collectives during epithelial wound healing.

The general progression of cancer drug development involves in vitro testing followed by safety and efficacy evaluation in clinical trials. Due to the expense of bringing candidate drugs to trials, in vitro models of cancer cells and tumor biology are required to screen drugs. There are many examples of drugs exhibiting cytotoxic behavior in cancer cells in vitro but losing efficacy in vivo, and in many cases, this is the result of poorly understood chemoresistant effects conferred by the cancer microenvironment. To address this, improved methods for culturing cancer cells in biomimetic scaffolds have been developed; along the way, a great deal about the nature of cancer cell-extracellular matrix (ECM) interactions has been discovered. These discoveries will continue to be leveraged both in the development of novel drugs targeting these interactions and in the fabrication of biomimetic substrates for efficient cancer drug screening in vitro.