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

Brian B. Silver, Celeste M. Nelson

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Article number21
JournalFrontiers in Cell and Developmental Biology
Issue numberMAR
StatePublished - Mar 6 2018

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Developmental Biology


  • Bioelectricity
  • Mechanical stress
  • Mechanotransduction
  • Morphodynamics
  • Morphogenesis


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