Time-resolved ultrastructure of the cortical actin cytoskeleton in dynamic membrane blebs

Autor: Aleksandra S. Chikina, Tatyana Svitkina, Antonina Y. Alexandrova
Rok vydání: 2018
Předmět:
Zdroj: The Journal of Cell Biology
ISSN: 1540-8140
0021-9525
DOI: 10.1083/jcb.201806075
Popis: Chikina et al. show preferential initiation of blebbing at local cytoskeleton weaknesses at filopodial bases when blebbing is induced by Arp2/3 complex inhibition. They also use correlative platinum replica electron microscopy to characterize actin cytoskeleton architecture in blebs at different stages of their expansion–retraction cycle.
Membrane blebbing accompanies various cellular processes, including cytokinesis, apoptosis, and cell migration, especially invasive migration of cancer cells. Blebs are extruded by intracellular pressure and are initially cytoskeleton-free, but they subsequently assemble the cytoskeleton, which can drive bleb retraction. Despite increasing appreciation of physiological significance of blebbing, the molecular and, especially, structural mechanisms controlling bleb dynamics are incompletely understood. We induced membrane blebbing in human HT1080 fibrosarcoma cells by inhibiting the Arp2/3 complex. Using correlative platinum replica electron microscopy, we characterize cytoskeletal architecture of the actin cortex in cells during initiation of blebbing and in blebs at different stages of their expansion–retraction cycle. The transition to blebbing in these conditions occurred through an intermediate filopodial stage, whereas bleb initiation was biased toward filopodial bases, where the cytoskeleton exhibited local weaknesses. Different stages of the bleb life cycle (expansion, pausing, and retraction) are characterized by specific features of cytoskeleton organization that provide implications about mechanisms of cytoskeleton assembly and bleb retraction.
Graphical Abstract
Databáze: OpenAIRE