The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation

Abstract

Evolution exploits the physics of non-neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear "developmental pathways" are often inadequate explanations for dynamic large-scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but also for the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system-level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering.

Active Perception during Angiogenesis: Filopodia speed up Notch selection of tip cells in silico and in vivo

“…There is an initiative among leading biologists to reframe the notion of what it means to explain the causes of a biological event [66]. It has been suggested that the classic feed-forward view based on molecular and genetic pathways, particularly in the context of developmental biology, falls short of explaining the adaptability and plasticity of large scale anatomical pattern formation even when they accurately describe the interactions of the individual molecular components [9,67,68]. Recent proposals prescribe the basal cognitive lens [69]-a strategy based on exploiting the deep parallels between anatomical pattern regulation and aspects of cognition such as perception, memory, and learning to better model and ultimately control these processes.…”

Over a century of cancer research: Inconvenient truths and promising leads

“…This stance predicates that cells are like tiny computers run by a program [51][52][53][54][55][56][57][58]. The lack of a robust theoretical background to frame experiments and explanations has hindered the adoption of productive alternatives in the fields of experimental biology and cancer research for decades [22,[59][60][61].…”

Genetic Causation in Complex Regulatory Systems: An Integrative Dynamic Perspective

“…[ 1 ] have already highlighted the central issue of integrating gene regulatory networks and cellular–physical mechanisms (see also refs. [43,75–78]). Areas of biology such as developmental genetics are dominated by an explanatory mode in which mechanism is identified with gene regulatory networks.…”