Epithelial tissues line all the organs of our body and function as physical barriers, thus, protecting the
underlying organs from infections, and aiding in the absorption of nutrients and gases from the food. Cells
within the epithelia perform these tasks, being jammed in a steady homeostatic density with little or no
apparent movement. Interestingly, the same cells unjam and almost flow like a fluid to migrate to relatively
long distances during physiological and pathological situations such as organ development, wound healing
and cancer metastasis. During such migratory events, cells within the epithelia display spectacular
coordination in movement and often require formation of Leader-cells at the migration front. How do cells
sense and transduce guidance signals along their neighbours? How, from a seemingly uniform epithelia, a
few cells become leaders? and How are the leader cells regulated in space and time? On the basis of our
recent work on collective cell migration[1, 2], I will try to address some of these questions and summarize
our current understanding on mechano-biology of epithelial wound healing. Conceptually, I will try to
defend the role of cooperative forces in instructing wound closure and extrapolate our findings to suggest
that epithelial tissues inherently, are characterized by cellular dynamics that allow for efficient wound
healing.
Towards the end, I will focus on my ongoing work on cell-competition within epithelial tissues.
Cell-competition is an important surveillance mechanism during tissue maintenance, where misfit cells
(losers) are recognized, and removed by neighbouring healthy cells (winners). Recent studies reveal that
cell competition also has a dark side and is exploited by cancer cells to grow and expand at the expense of
the host cells[3]. For example, in the context of skin cancer originating from p53-/- mutations and UV
radiation, mutant/cancer cells use mechanical compaction to kill the surrounding host cells, however, the
underlying molecular mechanism remained elusive. I will present our findings on how losers (wild type cells)
sense mechanical compaction from the winners (p53-/- cells) and how it leads to loser cell death.
I will pitch that cooperation and conflict management within epithelial tissues not only instruct
physiological functions, for e.g. tissue- repair and Epithelial defense against cancer, but also dictate pathological
situations such as tumour formation and metastasis and is therefore central to many fundamental biological
questions.
1. Vishwakarma, M., Di Russo, J., Probst, D., Schwarz, U.S., Das, T., and Spatz, J.P. (2018). Mechanical
interactions among followers determine the emergence of leaders in migrating epithelial cell
collectives. Nat Commun 9, 3469.
2. Vishwakarma, M., Thurakkal, B., Spatz, J.P., and Das, T. (2020). Dynamic heterogeneity influences
leader-follower dynamics during epithelial wound closure. Philosophical Transactions of Royal
Society-B.
3. Vishwakarma, M., and Piddini, E. (2020). Outcompeting cancer. Nat Rev Cancer.