title: Aging increases stiffness of cardiac myocytes measured by atomic force microscopy nanoindentation.
abstract: It is well established that the aging heart exhibits left ventricular (LV) diastolic dysfunction and changes in mechanical properties, which are thought to be due to alterations in the extracellular matrix. We tested the hypothesis that the mechanical properties of cardiac myocytes significantly change with aging, which could contribute to the global changes in LV diastolic dysfunction. We used atomic force microscopy (AFM), which determines cellular mechanical property changes at nanoscale resolution in myocytes, from young (4 mo) and old (30 mo) male Fischer 344 x Brown Norway F1 hybrid rats. A measure of stiffness, i.e., apparent elastic modulus, was determined by analyzing the relationship between AFM indentation force and depth with the classical infinitesimal strain theory and by modeling the AFM probe as a blunted conical indenter. This is the first study to demonstrate a significant increase (P < 0.01) in the apparent elastic modulus of single, aging cardiac myocytes (from 35.1 +/- 0.7, n = 53, to 42.5 +/- 1.0 kPa, n = 58), supporting the novel concept that the mechanism mediating LV diastolic dysfunction in aging hearts resides, in part, at the level of the myocyte.
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07101-1709, USA.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Lieber
authors.forename: Nadine
authors.initials: N
authors.lastname: Aubry
authors.forename: Jayashree
authors.initials: J
authors.lastname: Pain
authors.forename: Gissela
authors.initials: G
authors.lastname: Diaz
authors.forename: Song-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D004548:Elasticity; D004867:Equipment Design; D008297:Male; D018625:Microscopy, Atomic Force / Q000295:instrumentation; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley