The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been a...The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been applied to modulate almost all aspects of cell behavior, from cell adhesion and spreading to proliferation and differentiation. Delineation of the biophysical modulation of cell behavior is critical to the rational design of new biomaterials, implants, and medical devices. The effects of stiffness and topographical cues on cell behavior have previously been reviewed, respectively; however, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described, despite similarities in phenotypic manifestations. Herein, we first review the effects of substrate stiffness and nanotopography on cell behavior, and then focus on intracellular transmission of the biophysical signals from integrins to nucleus. Attempts are made to connect extracellular regulation of cell behavior with the biophysical cues. We then discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine.展开更多
3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(P...3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.展开更多
基金The authors would like to acknowledge funding support for Yong Yang from the National Science Foundation (CBET 1511759) and the National Institute of Health (NIH) (R15GM122953), and for Kam W. Leong from NIH (HL109442, AI096305, GMl10494, and UH3 TR000505), Guangdong Innovative and Entrepreneurial Research Team Program (2013S086), and the Global Research Laboratory Program (Korean NSF GRL 2015032163).
文摘The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been applied to modulate almost all aspects of cell behavior, from cell adhesion and spreading to proliferation and differentiation. Delineation of the biophysical modulation of cell behavior is critical to the rational design of new biomaterials, implants, and medical devices. The effects of stiffness and topographical cues on cell behavior have previously been reviewed, respectively; however, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described, despite similarities in phenotypic manifestations. Herein, we first review the effects of substrate stiffness and nanotopography on cell behavior, and then focus on intracellular transmission of the biophysical signals from integrins to nucleus. Attempts are made to connect extracellular regulation of cell behavior with the biophysical cues. We then discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine.
基金supported by the National Natural Science Foundation of China(Nos.22034005,81973569,and 21621003).
文摘3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.