Environmentally dependent and independent control of 3D cell shape.
Date
2024-05-28Author
Dent, LG
Curry, N
Sparks, H
Bousgouni, V
Maioli, V
Kumar, S
Munro, I
Butera, F
Jones, I
Arias-Garcia, M
Rowe-Brown, L
Dunsby, C
Bakal, C
Type
Journal Article
Metadata
Show full item recordAbstract
How cancer cells determine their shape in response to three-dimensional (3D) geometric and mechanical cues is unclear. We develop an approach to quantify the 3D cell shape of over 60,000 melanoma cells in collagen hydrogels using high-throughput stage-scanning oblique plane microscopy (ssOPM). We identify stereotypic and environmentally dependent changes in shape and protrusivity depending on whether a cell is proximal to a flat and rigid surface or is embedded in a soft environment. Environmental sensitivity metrics calculated for small molecules and gene knockdowns identify interactions between the environment and cellular factors that are important for morphogenesis. We show that the Rho guanine nucleotide exchange factor (RhoGEF) TIAM2 contributes to shape determination in environmentally independent ways but that non-muscle myosin II, microtubules, and the RhoGEF FARP1 regulate shape in ways dependent on the microenvironment. Thus, changes in cancer cell shape in response to 3D geometric and mechanical cues are modulated in both an environmentally dependent and independent fashion.
Collections
Subject
CP: Cell biology
FARP1
OPM
RhoGEF
TIAM2
cell protrusions
collagen
imaging 3D morphology
melanoma
microenvironment
oblique plane microscopy
Humans
Guanine Nucleotide Exchange Factors
Cell Shape
Cell Line, Tumor
Microtubules
Myosin Type II
Rho Guanine Nucleotide Exchange Factors
Melanoma
Research team
Dynamical Cell Systems
Language
eng
Date accepted
2024-03-14
License start date
2024-05-28
Citation
Cell Reports, 2024, 43 (5), pp. 114016 -
Publisher
CELL PRESS