Modulation of host cell mechanics by Trypanosoma cruzi.
To investigate the effects of Trypanosoma cruzi on the mechanical properties of infected host cells, cytoskeletal stiffness and remodeling dynamics were measured in parasite-infected fibroblasts. We find that cell stiffness decreases in a time-dependent fashion in T. cruzi-infected human foreskin fibroblasts without a significant change in the dynamics of cytoskeletal remodeling. In contrast, cells exposed to T. cruzi secreted/released components become significantly stiffer within 2 h of exposure and exhibit increased remodeling dynamics. These findings represent the first direct mechanical data to suggest a physical picture in which an intact, stiff, and rapidly remodeling cytoskeleton facilitates early stages of T. cruzi invasion and parasite retention, followed by subsequent softening and disassembly of the cytoskeleton to accommodate intracellular replication of parasites. We further suggest that these changes occur through protein kinase A and inhibition of the Rho/Rho kinase signaling pathway. In the context of tissue infection, changes in host cell mechanics could adversely affect the function of the infected organs, and may play an important role on the pathophysiology of Chagas' disease.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Adam
A
Mott
Guillaume
G
Lenormand
Jaime
J
Costales
Jeffrey J
JJ
Fredberg
Barbara A
BA
Burleigh
D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology*; D006790:Host-Parasite Interactions / Q000187:drug effects; D006801:Humans; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism
D000199:Actins; D047630:Depsipeptides; D018994:Myosin Light Chains; C057531:jasplakinolide; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases