Regulation of cell-cell fusion by nanotopography.
Cell-cell fusion is fundamental to a multitude of biological processes ranging from cell differentiation and embryogenesis to cancer metastasis and biomaterial-tissue interactions. Fusogenic cells are exposed to biochemical and biophysical factors, which could potentially alter cell behavior. While biochemical inducers of fusion such as cytokines and kinases have been identified, little is known about the biophysical regulation of cell-cell fusion. Here, we designed experiments to examine cell-cell fusion using bulk metallic glass (BMG) nanorod arrays with varying biophysical cues, i.e. nanotopography and stiffness. Through independent variation of stiffness and topography, we found that nanotopography constitutes the primary biophysical cue that can override biochemical signals to attenuate fusion. Specifically, nanotopography restricts cytoskeletal remodeling-associated signaling, which leads to reduced fusion. This finding expands our fundamental understanding of the nanoscale biophysical regulation of cell fusion and can be exploited in biomaterials design to induce desirable biomaterial-tissue interactions.
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Jagannath
J
Padmanabhan
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Michael J
MJ
Augelli
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Bettina
B
Cheung
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Mechanical Engineering and Materials Science, Yale University, New Haven, CT 06520, USA.|IBM Semiconductor Research and Development Center/IBM Corporate Patent Engineer, IBM, Hopewell Junction, New York 12533, United States.
Emily R
ER
Kinser
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Barnett
B
Cleary
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Priyanka
P
Kumar
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Renhao
R
Wang
Department of Pathology, Yale University, New Haven, CT 06520, USA.
Andrew J
AJ
Sawyer
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Rui
R
Li
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Mechanical Engineering and Materials Science, Yale University, New Haven, CT 06520, USA.
Udo D
UD
Schwarz
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Mechanical Engineering and Materials Science, Yale University, New Haven, CT 06520, USA.
Jan
J
Schroers
Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.|Dept. of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.|Department of Pathology, Yale University, New Haven, CT 06520, USA.
Themis R
TR
Kyriakides
D000537:Aluminum Oxide / Q000737:chemistry; D000818:Animals; D018929:Cell Culture Techniques; D002459:Cell Fusion; D002460:Cell Line; D003470:Culture Media; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D003470:Culture Media; D048051:p38 Mitogen-Activated Protein Kinases; D000537:Aluminum Oxide