Optical manipulation reveals macrophage mediated mesoscale brain mechanical homeostasisin vivo

Abstract

AbstractTissues are active materials where epithelial turnover, immune surveillance and remodeling of stromal cells such as macrophages all regulate form and function. There is a long-standing interest in harnessing the mechanical properties as a readout of tissue function. Optical techniques can provide the ability to assess the interplay between function, form and the measured mechanical properties in living tissues. However,in vivomicroscale longitudinal mapping of entire tissues remains challenging. Here, we employed optical tweezer active microrheology and Brillouin microscopy to address two questions: a) how do we reconcile methods to probe mechanical properties of mm tissues with sub cellular resolution? and b) how do we link the measured mechanical properties to stromal mediated-tissue homeostasis? We determined that the corrected Longitudinal modulus measured using Brillouin microscopy correlated well with shear modulus obtained from the optical tweezer measurements at lower frequencies. We determined that the brain tissue mechanical properties are dependent on both the structural presence of the macrophages and the CSF1R receptor that facilitates stromal remodeling linking mechanical measurements of Brillouin microscopy to biological determinants. Ablation of macrophages altered mechanical properties concomitantly with neural structures. Moreover, tissue mechanics and architecture do not return to those of unperturbed age-matched control animals after transient ablation has been resolved. Thus, consideration of the contribution of macrophage remodeling in the maintenance of mechanical homeostasis may be needed to harness macrophage-based therapeutics in disease management.