Pulsations and flows in tissues: two collective dynamics with simple cellular rules

Abstract

Epithelial cells flows are observed both in vivo and in vitro and are essential for morphogenesis. Here, we show that pulsatile flows involving local contraction and expansion of a tissue can arise in vitro in an epithelial monolayer of Madine Darby Canine Kidney (MDCK) cells. The strength of pulsation can be modulated through friction heterogeneity by observing the monolayer dynamics on micro-contact printed fibronectin grids with dimensions matching the length-scale of spontaneous oscillations. We also report pulsations by inducing wound closure in domains of similar size with micro-fabricated pillars. In contrast, strongly coherent flows can be induced by adding and washing out acto-myosin cytoskeleton inhibitors. To gain insight into the associated cellular mechanisms, we fluorescently label actin and myosin. We find that lamellipodia align with the direction of the flow, and tissue-scale myosin gradients arise during pulsations in wound-healing experiments. Pulsations and flows are recapitulated in silico by a vertex model with cell motility and polarisation dynamics. The nature of collective movements depends on the interplay between velocity alignment and random diffusion of cell polarisation. When they are comparable, a significant pulsatile flow emerges, whereas the tissue undergoes long-range flows when alignment dominates. We conjecture that the interplay between lamellipodial motile activity and cell polarization, with a possible additional role for tissue-scale myosin gradients, is at the origin of the pulsatile nature of the collective flow. Altogether, our study reveals that monolayer dynamics is dictated by simple rules of interaction at cellular levels which could be involved in morphogenesis.

Interplay between cell height variations and planar pulsations in epithelial monolayers

“…The experimentally observed pulsations in epithelial monolayers could be quantified in terms of the velocity divergence of the tissue flow that captures the dynamics of area expansion and contraction of tissue domains. It was also observed earlier [17] that myosin contractility was associated with these collective deformation modes of the monolayer. Hence, we now develop a simple continuum model with cell area a , contractile matter ζ , and velocity field v as three variables that are functions of x, y , and t .…”

“…In our previous work [17], we had studied pulsations on epithelial monolayers. Here, similar to the power spectrum S d ( ω ) and S d ( q ) for the divergence of pulsatory cellular movements on patterned surfaces discussed in Section 3.3 and plotted in figs.…”

“…Length scales of oscillations span from molecular assemblies of proteins to group of cells in tissues [11–15]. Similarly, the periods of oscillations scale from seconds to hours [16, 17]. Several studies using experiments and theory have explored the biological pathways and the under-lying molecular actors [18–20].…”

“…Several theoretical models, both discrete and continuum, have been developed to get insights into different aspects of tissue pulsations and wave propagation [27–29]. The discrete descriptions include active vertex [17, 26] and cellular phase field models [24], whereas the active continuum frameworks use underlying viscous or elastic rheology of the tissue to model the phenomena [23, 28]. The non-equilibrium activity is implemented in these models using cell polarity, motility, and active stress [30].…”

Interplay between cell height variations and planar pulsations in epithelial monolayers

“…Length scales of oscillations span from molecular assemblies of proteins to group of cells in tissues [11][12][13][14][15]. Similarly, the periods of oscillations scale from seconds to hours [16,17].…”