Under physiological and pathological conditions, cells experience large forces and deformations that often exceed the linear viscoelastic regime. Here we drive CD34 + cells isolated from healthy and leukemic bone marrows in the highly nonlinear elasto-plastic regime, by poking their perinuclear region with a sharp AFM cantilever tip. We use the wavelet transform mathematical microscope to identify singular events in the force-indentation curves induced by local rupture events in the cytoskeleton (CSK). We distinguish two types of rupture events, brittle failures likely corresponding to irreversible ruptures in a stiff and highly cross-linked CSK and ductile failures resulting from dynamic cross-linker unbindings during plastic deformation without loss of CSK integrity. We propose a stochastic multiplicative cascade model of mechanical ruptures that reproduces quantitatively the experimental distributions of the energy released during these events, and provides some mathematical and mechanistic understanding of the robustness of the log-normal statistics observed in both brittle and ductile situations. We also show that brittle failures are relatively more prominent in leukemia than in healthy cells suggesting their greater fragility.
Bibliographical noteWe are indebted to L Berguiga, E Gerasimova-Chechkina, C Martinez-Torres, L Streppa, R Vincent and T Voeltzel for fruitful discussions. We are very grateful to T Muller and to the R&D department of the JPK Company for their partnership. This study was supported by the Joliot Curie and Physics Laboratories (ENS Lyon/CNRS), the Agence Nationale de la Recherche ANR-10-BLAN-1516, INSERM (Plan Cancer 2012 01-84862), Novartis, Ligue Nationale contre le Cancer (Saone et Loire) and Cent pour Cent la Vie. FJPR acknowledges financial support from the Carnegie Trust.
- nanoindentation AFM technique
- cell mechanics
- actin cytoskeleton
- ductile and brittle failures
- log-normal statistics
- rupture cascade model
- chronic myelogenous leukemia