Division of Biology and Medicine
Center for Alternatives to Animals in Testing

Hyper-Compliant Microparticles

To improve our fundamental and quantitative understanding of tissue assembly, the Darling lab is using their hypercompliant microparticles to study how cellular-level forces change as human adult stem cells undergo mesenchymal condensation and maturation in 3D microtissues.

Hypercompliant Microparticles as Mechanical Sensors

  • The Darling Lab has developed small spherical microparticles the size of a single cell that act as small mechanical sensors. These synthetic microparticles are very soft (hyper-compliant).
  • When added to a living 3D microtissue, the microparticles become embedded in the microtissue and the cells exert small forces that cause deformations to the size and shape of the microparticles.
  • We have utilized the Opera Phenix high-content imaging system to acquire 3D images of the deformed microparticles embedded in the microtissue.
  • Because the stiffness of the hypercompliant microparticles are well defined, we can analyze the images of the deformed microparticles and calculate the magnitude of the small forces that the cells are exerting.
  • In addition to the size of the forces, we can calculate the direction of these cell-generated forces. In this way, we can quantitatively assess the local mechanical environments in both simple and complex systems at the cellular level without disrupting the larger behavior of the microtissue.
  • Cell forces are critical for many biological processes including early development and tissue differentiation and can be altered in certain pathological environments.
  • To improve our fundamental and quantitative understanding of tissue assembly, we are using their hypercompliant microparticles to study how cellular-level forces change as human adult stem cells undergo mesenchymal condensation and maturation in 3D microtissues.

Learn More

Labriola, NR., Mathiowitz, E, Darling, E M. (2016). Fabricating polyacrylamide microbeads by inverse emulsification to mimic the size and elasticity of living cells. Biomaterials science5(1), 41-45. PMC5201106

Labriola, N.R., Sadick, J.S., Morgan, J.R., Mathiowitz, E., Darling, E.M. (2018). Cell mimicking microparticles influence the organization, growth, and mechanophenotype of stem cell spheroids. Annals of Biomedical Engineering, 46(8), 1146-1159. PMC6039261

Labriola, N.R., Azagury, A., Gutierrez, R., Mathiowitz, E., Darling, E.M. (2018). Concise review: Fabrication, customization, and application of cell mimicking microparticles in stem cell science. Stem Cell Translational Medicine, 7(2), 232-240. PMC5788880

Shah, M.K., Leary, E.A., Darling, E.M. (2019). Integration of hyper-compliant microparticles into a 3D melanoma tumor model. Journal of Biomechanics, 82, 46-53. PMC6310620.

Investigators