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This article is part of the Research Topic

Microenvironment in Disease and Aging

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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2018.00021

The bioelectric code: reprogramming cancer and aging from the interface of mechanical and chemical microenvironments

Brian B. Silver1 and  Celeste M. Nelson1*
  • 1Princeton University, United States

Cancer is a complex, heterogeneous group of diseases that can develop through many routes. Broad treatments such as chemotherapy destroy healthy cells in addition to cancerous ones, but more refined strategies that target specific pathways are usually only effective for a limited number of cancer types. This is largely due to the multitude of physiological variables that differ between cells and their surroundings. It is therefore important to understand how nature coordinates these variables into concerted regulation of growth at the tissue scale. The cellular microenvironment might then be manipulated to drive cells toward a desired outcome at the tissue level. One unexpected parameter, cellular membrane voltage (Vm), has been documented to exert control over cellular behavior both in culture and in vivo. Manipulating this fundamental cellular property influences a remarkable array of organism-wide patterning events, producing striking outcomes in both tumorigenesis as well as regeneration. These studies suggest that Vm is not only a key intrinsic cellular property, but also an integral part of the microenvironment that acts in both space and time to guide cellular behavior. As a result, there is considerable interest in manipulating Vm both to treat cancer as well as to regenerate organs damaged or deteriorated during aging. However, such manipulations have produced conflicting outcomes experimentally, which poses a substantial barrier to understanding the fundamentals of bioelectrical reprogramming. Here, we summarize these inconsistencies and discuss how the mechanical microenvironment may impact bioelectric regulation.

Keywords: Mechanotransduction, bioelectricity, Morphodynamics, Mechanical Stress, Morphogenesis

Received: 06 Dec 2017; Accepted: 15 Feb 2018.

Edited by:

Derek C. Radisky, Mayo Clinic, United States

Reviewed by:

Ren Xu, University of Kentucky, United States
Amit Pathak, Washington University in St. Louis, United States  

Copyright: © 2018 Silver and Nelson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Celeste M. Nelson, Princeton University, Princeton, United States,