TY  - JOUR
A1  - Barbosa Pfannes, Eva Katharina
A1  - Theves, Matthias
A1  - Wegner, Christian
A1  - Beta, Carsten
T1  - Impact of the carbazole derivative wiskostatin on mechanical stability
 and dynamics of motile cells
JF  - JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
N2  - Many essential functions in eukaryotic cells like phagocytosis, division, and motility rely on the dynamical properties of the actin cytoskeleton. A central player in the actin system is the Arp2/3 complex. Its activity is controlled by members of the WASP (Wiskott-Aldrich syndrome protein) family. In this work, we investigated the effect of the carbazole derivative wiskostatin, a recently identified N-WASP inhibitor, on actin-driven processes in motile cells of the social ameba . Drug-treated cells exhibited an altered morphology and strongly reduced pseudopod formation. However, TIRF microscopy images revealed that the overall cortical network structure remained intact. We probed the mechanical stability of wiskostatin-treated cells using a microfluidic device. While the total amount of F-actin in the cells remained constant, their stiffness was strongly reduced. Furthermore, wiskostatin treatment enhanced the resistance to fluid shear stress, while spontaneous motility as well as chemotactic motion in gradients of cAMP were reduced. Our results suggest that wiskostatin affects the mechanical integrity of the actin cortex so that its rigidity is reduced and actin-driven force generation is impaired.
KW  - Actin dynamics
KW  - Wiskostatin
KW  - Dictyostelium discoideum
Y1  - 2012
U6  - https://doi.org/10.1007/s10974-012-9287-8
SN  - 0142-4319
VL  - 33
IS  - 2
SP  - 95
EP  - 106
PB  - SPRINGER
CY  - DORDRECHT
ER  -