TY - JOUR
T1 - On the origins of the universal dynamics of endogenous granules in mammalian cells
AU - Vanapalli, Siva A.
AU - Li, Yixuan
AU - Mugele, Frieder
AU - Duits, Michel H.G.
PY - 2009
Y1 - 2009
N2 - Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics - both of which are crucial for the interpretation of the results from MPTM technique - are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms - molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dy-namics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.
AB - Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics - both of which are crucial for the interpretation of the results from MPTM technique - are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms - molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dy-namics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.
KW - Actinmyosin contractility
KW - Cytoskeleton
KW - Microrheology
KW - Microtubule polymerization
KW - Molecular motor
UR - http://www.scopus.com/inward/record.url?scp=73949106574&partnerID=8YFLogxK
M3 - Article
C2 - 19899443
AN - SCOPUS:73949106574
SN - 1556-5297
VL - 6
SP - 191
EP - 201
JO - MCB Molecular and Cellular Biomechanics
JF - MCB Molecular and Cellular Biomechanics
IS - 4
ER -