An EPFL (Ecole Polytechnique Federale de Lausanne) team led by professor Melody Swartz has demonstrated for the first time that the presence of very slow biological flows affects the extracellular environment in ways that are critical for tissue formation and cell migration.
Their results will appear online the week of October 24 in Proceedings of the National Academy of Sciences.
A major challenge for tissue engineering is to identify the essential environmental ingredients that cells need in order to communicate, migrate, and organize into living tissues. One of these ingredients is the presence, outside the cell, of minute changes in the concentration of special proteins called morphogens. Cells can sense even the tiniest differences in morphogen concentration and will alter their functions accordingly. In embryonic development, stem cells differentiate into organs by means of the actions of morphogens. And even cancer cells can use morphogens to grow, induce a blood supply, and metastasize.
Although the concept of cell organization in response to these morphogen gradients is well documented, little is known about how these subtle concentration changes get established the first place, particularly within the dynamic environment of a real tissue. This research provides evidence that tiny biophysical forces in the extracellular environment may play an important role.
Swartz and her colleagues have found that slow biophysical flows, such as the slow-moving flows that exist between the lymphatic and blood capillaries to help transport macromolecules from blood to tissues, play an important role in the formation of these gradients. They used a computational model developed by PhD student Mark Fleury to demonstrate that in the presence of a slow moving flow, cells can set up and even amplify their own morphogen gradients. "This exquisite system may have evolved as a way for cells to gain better control of their local extracellular surroundings, where they can use the fluid forces that exist in tissues to direct and amplify communication and organization," explains Swartz.