“We live in a physical world and every single molecule within your cells and every tissue is subjected to some level of force. Not to appreciate that this plays an intimate role in cell biology and tissue physiology and development is at our own peril,” said Valerie Weaver, Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery at the University of California, San Francisco.
Weaver serves as the lead editor for the sixth edition of a special issue on Forces On and Within Cells published by ASCB’s basic science research journal Molecular Biology of the Cell. Articles can be submitted until March 1. Co-editors include Dennis Discher (University of Pennsylvania), Alex Dunn (Stanford), Michael Murrell (Yale University), and Alpha Yap (University of Queensland).
Although trained as a biochemist, Weaver wasn’t slow to recognize how important physical forces were to cells, but it has taken a while for the field to come into its own. Weaver said that when cell biologists first started more widely incorporating the physical sciences in their studies, it was considered to be somewhat of a novelty. However, that is no longer the case. Weaver believes that developmental biologists were likely the first group to take forces into account because their studies examine complex interactions in tissues and live animals.
“When cell biologists first started to study the role of mechanical forces on cells, the studies were rather basic,” Weaver said. “But as the field has matured, so too has our understanding of the nuances of how force regulates everything from chromatin to transcription, and transport and various cell biological processes, to tissue physiology, development, and disease.” Weaver said she looks forward to reviewing the submitted papers that feature cutting-edge technologies and new insights on how the study of forces could broaden our understanding of other aspects of cell biology.
Weaver noted that researchers are developing more sophisticated ways to measure cell traction force in a 3D context. She said the signal-to-noise ratio on force sensors has improved. And she added that she is particularly excited about new work on the effects on the cell of forces transmitted in and to the nucleus.
Since forces are not uniform across length scales, Weaver said, she is “interested in bringing this work in vivo for [studies on] development and disease. Because that is where we will have a very good outreach to colleagues in other fields.”
Complexity increases, however, from the picoNewton force measurements at the molecular level (enough to unfold a protein) to the longer length scales of tissues and organs. Furthermore, the heterogeneity of cell populations within tissues and organs also presents challenges.
For example, comprehending the forces generated from calcium-regulated ion channels might seem straightforward, she said. “Activation of the calcium ion channel elicits a signal,” Weaver said, “but then it becomes really complicated. [Then] you have signal transduction and then you have other effects, which could influence cell contractility, which could have pleotropic effects in the cell.”
In the future, she hopes that research on cell forces becomes more accessible so that more people will get involved. The application of artificial intelligence and machine learning will help increase access to those lacking costly wet lab equipment.
“I will have failed if I don’t make my research accessible to others,” Weaver said. “I know I sound like a zealot, but I truly believe it’s important!”
The complete interview with Valerie Weaver about forces and cell biology is featured in the Pathways Podcast. Listen here: https://bit.ly/3unILyB.
About the Author:
Mary Spiro is ASCB's Strategic Communications Manager.