During development, animal cells carry out incredible architectural feats, including making collagen fibers and using them to build ligaments, tendons, and other complex structures. Researchers have now shown that mechanical forces can drive the crystallization of collagen to form fibers (ACS Nano 2016, DOI: 10.1021/acsnano.5b07756). The finding may provide insight into how cells build structures in the body and help tissue engineers develop new ways to make collagen for new corneas or to mend spinal disc injuries.
Collagen, found just about everywhere in the body, provides structural support. During development, cells put together short, peptide-based collagen building blocks. Cells build these into fibers and structures much larger than the cells themselves, using a poorly understood assembly process involving structures on their membrane surfaces. Bioengineers’ attempts to mimic this process haven’t worked too well so far, says Jeffrey W. Ruberti of Northeastern University.
Because previous studies have shown that tension makes collagen more stable at the macroscale, Ruberti hypothesized that mechanical forces may play a role during the collagen-building process. So he set out to test the effects of tiny, cell-scale strains on collagen building blocks at life-like concentrations.
Working with a solution of collagen peptides, Ruberti and colleagues dipped a microneedle into a droplet and slowly pulled it out, drawing the liquid with it and forming a collagen fiber. Some of the fibers they made were longer than 10 mm. If they drew the needle too quickly, the fiber broke, though it could be repaired by dipping the end back into the droplet and pulling it out again slowly. Transmission electron microscopy of the fibers showed that they were aligned to a similar degree as in natural collagen fibers found in biological structures like tendons.
This tendency of flow to encourage the formation of well-aligned fibers is called flow-induced crystallization, an effect known to industrial chemists. Under the right conditions, applying strain to a liquid solution of precursors—for example, by flowing that liquid down a narrowing channel—can drive them to align and start forming fibers. Ruberti says that since his experiment was done at strains small enough for a cell to apply, cells probably do take advantage of strain to build collagen fibers.
Karl E. Kadler, a biochemist at the University of Manchester who studies how cells build with collagen, says there aren’t enough data to say anything about whether cells in the developing body use flow-induced crystallization to form collagen fibers. Whatever it is biological cells do, Ruberti says these biophysical strain data may be useful to tissue engineers as a way to build fibers.