8th Annual Symposium
Physics of Cancer
October 4-6, 2017
|PoC - Physics of Cancer - Annual Symposium|
Guiding 3D cell migration inside strained synthetic hydrogel micro-structures
The mechanical properties of the extracellular matrix are fundamental guidance cues for cell migration in 3D. To prevent cross-signaling of different stimuli present in naturally derived hydrogels, synthetic hydrogels with a defined composition and therefore reduced complexity are often used to analyze the underlying mechanisms of directed cell migration. We are interested in how static strains in these matrices influence migration of embedded HT-1080 cells.
We use a novel method to introduce uniaxial static strain in matrices. In a photo-induced polymerization reaction, a polyethylene glycol (PEG) based hydrogel, functionalized with small peptide sequences, is micro-structured in thin strips via simple photolithography inside a channel slide. Due to the confinement of the channel, hydrogel strips swell anisotropically, thereby inducing uniaxial strain in the network. Embedded HT-1080 cells show a highly anisotropic migration response parallel to the strain direction, with maximal anisotropy at intermediate strain levels. We can account for this non-monotonic response with a theoretical model of a durotactic cell on a 2.5 D lattice performing proteolytic migration. Straining of this lattice results in anisotropic movement of the cell similar to the experimental result.
Our model shows that a geometric anisotropic stiffening of the meshwork on the microscale due to the macroscopically applied strain, can act as a guidance cue for directed cell migration. This work highlights that it is crucial to consider the network properties on the cellular scale when trying to find the guidance cues that are most important for cell behavior.