Abstract
The reaction and diffusion of morphogens is a mechanism widely used to explain many spatial patterns in physics, chemistry and developmental biology. However, because experimental control is limited in most biological systems, it is often unclear what mechanisms account for the biological patterns that arise. Here, we study a biological model of cultured vascular mesenchymal cells (VMCs), which normally self-organize into aggregates that form into labyrinthine configurations. We use an experimental control and a mathematical model that includes reacting and diffusing morphogens and a third variable reflecting local cell density. With direct measurements showing that cell motility was increased ninefold and threefold by inhibiting either Rho kinase or non-muscle myosin-II, respectively, our experimental results and mathematical modelling demonstrate that increased motility alters the multicellular pattern of the VMC cultures, from labyrinthine to a pattern of periodic holes. These results suggest implications for the tissue engineering of functional replacements for trabecular or spongy tissue such as endocardium and bone.
Highlights
Morphogenesis consists of local activities that contribute collaboratively to global pattern formation
We found that experimental increases in ‘random’ cell motility, whether by inhibition of Rho kinase (ROCK) or of non-muscle myosin-II (NMM-II), changed the pattern formation of these cultures from a labyrinthine pattern to a novel observation, a pattern of periodic holes. (The term ‘random motility’ is used in the literature to distinguish this kind of motility, which has no directional preference, from chemotactic motility, which is always in the preferred direction of chemical morphogen gradients.)
Our experiments provide an interesting further application of the Turing paradigm in biology with measurable parameters and experimental controls
Summary
Morphogenesis consists of local activities that contribute collaboratively to global pattern formation. We use cultured vascular mesenchymal cells (VMCs), stem cell-like multipotent cells that differentiate and self-organize into aggregates in labyrinthine and spot configurations by a Turing-like instability [9]. In these cultures, we are able to control and measure the parameters that govern cell motility. We found that experimental increases in ‘random’ cell motility, whether by inhibition of Rho kinase (ROCK) or of non-muscle myosin-II (NMM-II), changed the pattern formation of these cultures from a labyrinthine pattern to a novel observation, a pattern of periodic holes. With direct evidence showing how cellular activities interplay with the reaction and diffusion of chemical morphogens, our findings attempt to bridge the gap between cell physiology and tissue-level morphogenesis
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