Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion

Knode BK, Beeghly GF, Schutrum BE, Wang D, Zheng Y, Battistella A, Goswami R, Eom CY, Kopyeva I, Bozec A, Guck J, Nishimura N, Girardo S, O'Hern CS, Fischbach C (2026)

Publication Type: Journal article

Publication year: 2026

Article Number: 100411

DOI: 10.1016/j.celbio.2026.100411

Abstract

Breast cancer cells invade collagen type I-rich mammary adipose tissue during the initial stages of metastasis, but how adipocyte mechanics regulate this process remains unclear. To elucidate these connections, we quantified the size and stiffness of primary adipocytes and replicated these properties using tunable polyacrylamide (PAAm) beads. Subsequently, we embedded these beads into type I collagen to form 3D granular hydrogels mimicking native adipose tissue architecture. Bead-embedded hydrogels demonstrated increased breast cancer cell invasion and collagen fiber organization relative to beadless controls, and cells invaded more readily in systems with decreased bead stiffness. Similarly, discrete element method simulations revealed that soft beads promoted invasion by deforming in response to confined cancer cell migration. These trends were validated in vivo via intravital imaging of murine mammary tumors. Collectively, our data suggest that adipocyte mechanics regulate breast cancer invasion by coordinating both matrix architecture and cellular confinement.

Authors with CRIS profile

Aline Bozec Department of Medicine 3 – Rheumatology and Immunology Jochen Guck

Involved external institutions

Yale University US United States (USA) (US) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Cornell University US United States (USA) (US)

How to cite

APA:

Knode, B.K., Beeghly, G.F., Schutrum, B.E., Wang, D., Zheng, Y., Battistella, A.,... Fischbach, C. (2026). Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion. . https://doi.org/10.1016/j.celbio.2026.100411

MLA:

Knode, Brianna K., et al. "Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion." (2026).

BibTeX: Download