title: On the modelling of biological patterns with mechanochemical models: Insights from analysis and computation.
abstract: The diversity of biological form is generated by a relatively small number of underlying mechanisms. Consequently, mathematical and computational modelling can, and does, provide insight into how cellular level interactions ultimately give rise to higher level structure. Given cells respond to mechanical stimuli, it is therefore important to consider the effects of these responses within biological self-organisation models. Here, we consider the self-organisation properties of a mechanochemical model previously developed by three of the authors in Acta Biomater. 4, 613-621 (2008), which is capable of reproducing the behaviour of a population of cells cultured on an elastic substrate in response to a variety of stimuli. In particular, we examine the conditions under which stable spatial patterns can emerge with this model, focusing on the influence of mechanical stimuli and the interplay of non-local phenomena. To this end, we have performed a linear stability analysis and numerical simulations based on a mixed finite element formulation, which have allowed us to study the dynamical behaviour of the system in terms of the qualitative shape of the dispersion relation. We show that the consideration of mechanotaxis, namely changes in migration speeds and directions in response to mechanical stimuli alters the conditions for pattern formation in a singular manner. Furthermore without non-local effects, responses to mechanical stimuli are observed to result in dispersion relations with positive growth rates at arbitrarily large wavenumbers, in turn yielding heterogeneity at the cellular level in model predictions. This highlights the sensitivity and necessity of non-local effects in mechanically influenced biological pattern formation models and the ultimate failure of the continuum approximation in their absence.
authors.affiliation: Aragón Institute of Engineering Research, University of Zaragoza, Spain. pmoreo@unizar.es
authors.forename: P
authors.initials: P
authors.lastname: Moreo
authors.forename: E A
authors.initials: EA
authors.lastname: Gaffney
authors.forename: J M
authors.initials: JM
authors.lastname: García-Aznar
authors.forename: M
authors.initials: M
authors.lastname: Doblaré
mesh_terms: D000465:Algorithms; D000818:Animals; D001696:Biomechanical Phenomena; D019521:Body Patterning / Q000502:physiology*; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D003198:Computer Simulation; D005109:Extracellular Matrix / Q000502:physiology; D020342:Finite Element Analysis; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000502:physiology