AFM macro-probes to investigate whole 3D cardiac spheroids

• Main Authors: Andolfi, L. (Author), Lazzarino, M. (Author), Mestroni, L. (Author), Taylor, M.R.G (Author), Zanetti, M. (Author)
• Format: Article
• Language: English
• Published: Elsevier B.V. 2022
• Subjects: 3D models; 3d-modeling; AFM; Atomic force; Atomic force microscope; Cardiomyocytes; Dynamics properties; Elasticity; Mechanical measurements; Mechanobiology; Mechano-biology; Microfabrication; Probes; Rheology; Spheroid; Spheroids; Stress relaxation; Viscoelastics
• Online Access: View Fulltext in Publisher

 In its many applications, the Atomic Force Microscope (AFM) is a promising tool in cardiac mechanobiology because it can unravel the viscoelastic and mechano-dynamic properties of individual cardiomyocytes. However, the biophysical investigation of more accurate 3D models is hampered by commercial probes, which typically operate at the cell sub-compartmental resolution. We have previously shown how flat macro-probes can overcome these limitations by extending the AFM mechanical measurements to multicellular aggregates. Such macro-probes are fabricated by standard micromachining and carry a flat polymeric wedge to offset the AFM mounting tilt. Therefore, the AFM is upgraded to a micro-parallel plate rheometer with unmatched force range and sensitivity. In this article, we show how these macro-probes can be applied to reveal the global rheology of primary cardiomyocytes spheroids, by performing stress-relaxation tests. More importantly, we demonstrate that these macro-probes can be used as passive sensors capable of monitoring the spheroid beating force and beating pattern, and to perform a “micro-CPR” on the spheroid itself. © 2022 The Authors