Abstract
Cell motility in response to environmental cues forms the basis of many developmental processes in multicellular organisms. One such environmental cue is an electric field (EF), which induces a form of motility known as electrotaxis. Electrotaxis has evolved in a number of cell types to guide wound healing and has been associated with different cellular processes, suggesting that observed electrotactic behavior is likely a combination of multiple distinct effects arising from the presence of an EF. To determine the different mechanisms by which observed electrotactic behavior emerges, and thus to design EFs that can be applied to direct and control electrotaxis, researchers require accurate quantitative predictions of cellular responses to externally applied fields. Here, we use mathematical modeling to formulate and parameterize a variety of hypothetical descriptions of how cell motility may change in response to an EF. We calibrate our model to observed data using synthetic likelihoods and Bayesian sequential learning techniques and demonstrate that EFs bias cellular motility through only one of a selection of hypothetical mechanisms. We also demonstrate how the model allows us to make predictions about cellular motility under different EFs. The resulting model and calibration methodology will thus form the basis for future data-driven and model-based feedback control strategies based on electric actuation.
Highlights
Cell migration underpins key physiological processes central to developmental biology, as well as wound healing and tissue regeneration, and it plays a crucial role in invasive, metastatic cancers
In this paper we describe a parametrised stochastic model of the motile behaviour of a single human corneal epithelial cell, in which the cell’s motility is driven by an internal polarity, in combination with the external influence of a direct current (DC) electric field (EF)
The four means by which we model cell motility to be perturbed by the EF are: Velocity bias (γ1 ) The EF imparts an additional component of force on the cell
Summary
Cell migration underpins key physiological processes central to developmental biology, as well as wound healing and tissue regeneration, and it plays a crucial role in invasive, metastatic cancers. The cellular processes driving collective migration are complex and multifaceted, deriving from diverse physical mechanisms and various external stimuli [3], making it challenging for researchers to accurately and robustly direct cell motility. Due to the ease with which electric fields can be controlled and applied to cells, research into the control of cell motility has recently focused on exploiting electrotaxis. The precise effects of electric fields on intracellular processes and on cell motility are not fully understood, making quantitative predictions and control policy design impractical. Electrotactic cells have been observed to change their motile behaviour in response to the presence of a direct current (DC)
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