title: Fast Stiffness Mapping of Cells Using High-Bandwidth Atomic Force Microscopy.
abstract: The cytoskeleton controls cellular morphology and mediates the mechanical interactions between a cell and its environment. Atomic force microscopy (AFM) has the unique capability to map cytoskeletal mechanics and structures with nanometer resolution. However, whole-cell cytomechanical imaging with conventional AFM techniques is limited by low imaging speed. Here, we present fast nanomechanical mapping of cells using high-bandwidth AFM (HB-AFM), where >10(6) nanoindentation measurements were acquired in ∼10 min-a task that would take weeks to finish using conventional AFM. High-bandwidth measurements enabled capture of the entire tip-sample interaction for each tap on cells, engendering a new measurement ("force phase") that exceeds the contrast of conventional tapping mode and enabling spectral visualization of >10 harmonics. The abundance of measurements allowed discovery of subtle cytomechanical features, including the stiffness of fibers of the cellular spectrin network in situ. This approach bridges HB-AFM and high-harmonic imaging and opens future opportunities for measuring the dynamic mechanical properties of living cells.
authors.affiliation: Department of Pediatrics and ‡Department of Electrical Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Pediatrics and ‡Department of Electrical Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Karthik
authors.initials: K
authors.lastname: Vijayraghavan
authors.affiliation: Department of Pediatrics and ‡Department of Electrical Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Olav
authors.initials: O
authors.lastname: Solgaard
authors.affiliation: Department of Pediatrics and ‡Department of Electrical Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D016466:CHO Cells; D003412:Cricetulus; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure*; D006244:Hardness; D018625:Microscopy, Atomic Force / Q000295:instrumentation / Q000379:methods*; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure*; D013997:Time Factors
keywords: AFM; cells; harmonic; high-bandwidth; multifrequency