Abstract:
:The biophysical properties of extracellular matrices (ECM) are known to regulate cell behavior, however decoupling cell behavior changes due to the relative contributions of material microstructure versus biomechanics or nutrient permeability remains challenging, especially within complex, multi-material matrices. We developed four gelatin-fibrin interpenetrating network (IPN) formulations which are identical in composition but possess variable gelatin molecular weight distributions, and display differences in microstructure, biomechanics, and diffusivity. In this work we interrogate the response of multicellular tumor spheroids to these IPN formulations and found that a high stiffness, gelatin-network dominated IPNs impeded remodeling and invasion of multicellular tumor spheroids; whereas relatively lower stiffness, fibrin-network dominated IPNs permitted protease-dependent remodeling and spheroid invasion. Cell proliferation correlated to nutrient diffusivity across tested IPN formulations. These findings demonstrate the complexity of ECM IPNs, relative to single polymer matrices, and highlight that cell response does not derive from a single aspect of the ECM, but rather from the interplay of multiple biomechanical properties. The methodology developed here represents a framework for future studies which aim to characterize cellular phenotypic responses to biophysical cues present within complex, multi-material matrices.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Dubbin K,Robertson C,Hinckley A,Alvarado JA,Gilmore SF,Hynes WF,Wheeler EK,Moya MLdoi
10.1016/j.biomaterials.2020.120035subject
Has Abstractpub_date
2020-08-01 00:00:00pages
120035eissn
0142-9612issn
1878-5905pii
S0142-9612(20)30281-7journal_volume
250pub_type
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