Increasingly, disciplines like physics have found a home in research into biology — particularly research looking at the functioning of biological systems within and between cells.
Researchers working at UC Santa Barbara, including Samhita Banavar, a former graduate student in the department of physics who is now at Stanford University, Otger Campàs, with the California NanoSystems Institute, Michael Trogdon and Linda R. Petzold in the department of mechanical engineering and Tau-Mu Yi in the department of molecular, cell and developmental biology, in addition to Brian Drawert from the department of computer science at the University of North Carolina Asheville, exemplify this boundary-pushing way of thinking.
Their interdisciplinary work, published in PLOS ONE, devised a theoretical model which used physics to better understand morphogenesis, the process by which cells take shape.
“I’ve always been interested in morphogenesis, especially looking at it from a physics point of view, rather than the typical biology point of view,” Banavar said.
Banavar and her collaborators looked into the mating machinations of yeast cells, which have a rigid cell wall in addition to the cell membrane observed in normal animals cells. When yeast cells mate with other cells, they — lacking the ability to move to one another — grow projections in order to reach their soon-to-be mate. In essence, rather than move, yeast cells “stretch,” aided by the lure of pheromones.
She and her collaborators were interested in understanding how cells understand their own geometry, know where to grow and ultimately maintain polarization, the process in which the components within cells transition from a uniform distribution to a localized distribution for growth or movement.
“And so at the polarized region you can start growing, or you could start moving — sometimes movement is in a polarized fashion,” Banavar explained.
As yeast cells grow to meet their would-be mates, the cell wall at the site of polarization — the polarization cap, as Banavar and her collaborators describe — must add material at a rate comparable to the rate that the cell itself is expanding.
“The pressure inside the yeast cell is very high, and so it could very easily break that wall. And so the question becomes how does the cell coordinate. How does it say, ‘Oh, we need material at this location to grow the wall,’” Banavar said.
If the cell wasn’t able to maintain this, there would be dire consequences. For instance, some yeast cells which have been experimentally modified and are unable to grow in the manner they are supposed to end up “popping,” for instance. This gruesome fate, however, is not common by any means in nature.
Banavar and her collaborators believe they may have an answer for why that is.
Through theoretical modeling, the researchers discovered that cells require a feedback mechanism, one linking the cell’s rate of expansion and the rate by which the cell wall secretes material. There must be coordination between forces governing the cell as it expands.
In the absence of the mechanical feedback encoded in the cell, as described by Banavar and her collaborators model, cell polarity cannot be maintained, the yeast cell’s polarization cap moves away from the tip where growth is directed, and morphogenesis cannot continue. Tragically, the yeast cells remain a projection-length away, unable to mate, forever alone.
Drawing from previous research, Banavar and her collaborators looked toward a known biological pathway, the Cell Wall Integrity pathway, which encodes mechanical feedback in the cell genetically and is able to sense stress in the cell wall, providing the cell with the information needed to maintain cell polarization during growth.
Adding strong enough mechanical feedback, however, fixes this.
“We’re thinking that [the Cell Wall Integrity pathway] is the pathway that could solve this problem,” Banavar said. “Of course, it still does have to be experimentally proven.”
Even so, Banavar is interested to see how this work informs future research into similar mechanisms in other pathways and systems — not to mention future research into the Cell Wall Integrity pathway itself — especially as physics and physical mechanisms are increasingly identified as being important for biological systems.
“And so the physics of the system is quite interesting and should be studied along with the biology. Linking them through these mechanical feedbacks and seeing how the two kind of interplay is very interesting. I think it can help us understand morphogenesis in various systems — including multicellular tissues,” Banavar said.