한빛사논문 | BRIC

한빛사 논문

조회46

University of Western Australia

Adv. Healthc. Mater., Sep 05 2023 | https://doi.org/10.1002/adhm.202301506 3D Volumetric Mechanosensation of MCF7 Breast Cancer Spheroids in a Linear Stiffness Gradient GelagE.

Danielle Vahala ¹, Sebastian E Amos ¹, Marta Sacchi 1, Bram G Soliman ², Matt S Hepburn ³, Alireza Mowla ³, Jiayue Li ³, Ji Hoon Jeong ⁴, Chrissie Astell ¹, Yongsung Hwang ⁴, Brendan F Kennedy ³, Khoon S Lim ^2,5,6, Yu Suk Choi¹

¹School of Human Sciences, The University of Western Australia, Perth, Western Australia, 6009, Australia.

²Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, WA, 6009, Australia.

³BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, and Centre for Medical Research, The University of Western Australia, Perth, WA, 6009, Australia.

⁴Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do, 31151, South Korea.

⁵Department of Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago Christchurch, Christchurch, 8140, New Zealand.

⁶School of Medical Sciences, University of Sydney, Sydney, NSW, 2006, Australia.

CORRESPONDING AUTHOR : Yu Suk Choi

Abstract

The tumor microenvironment presents spatiotemporal shifts in biomechanical properties with cancer progression. Hydrogel biomaterials like GelAGE offer the stiffness tuneability to recapitulate dynamic changes in tumor tissues by altering photo-energy exposures. Here, we develop a tuneable hydrogel with spatiotemporal control of stiffness and mesh-network. The volume of MCF7 spheroids encapsulated in a linear stiffness gradient demonstrates an inverse relationship with stiffness (p < 0.0001). As spheroids are exposed to increased crosslinking (stiffer) and greater mechanical confinement, spheroid stiffness increases. Protein expression (TRPV4, β1 integrin, E-cadherin and F-actin) decrease with increasing stiffness while showing strong correlations to spheroid volume (r ² > 0.9). To further investigate the role of volume, MCF7 spheroids were grown in a soft matrix for 5 days prior to a second polymerisation which presents a stiffness gradient to equally expanded spheroids. Despite being exposed to variable stiffness, these spheroids showed even protein expression, confirming volume as a key regulator. Overall, this work showcases the versatility of GelAGE and demonstrates volume expansion as a key regulator of 3D mechanosensation in MCF7 breast cancer spheroids. This platform has the potential to further investigation into the role of stiffness and dimensionality in 3D spheroid culture for other types of cancers and diseases. This article is protected by copyright. All rights reserved.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-18)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

댓글 작성 로그인

CV 열람하기

연락처 보기