substrate rigidity dictates phenotype, survival, and...
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Substrate Rigidity Dictates Phenotype, Survival, and Substrate Rigidity Dictates Phenotype, Survival, and
Mechanics of Primary Human Osteosarcoma CellsMechanics of Primary Human Osteosarcoma Cells
Eleni Mylona1, Zoe H. Dailiana2, Xavier Trepat3, and Michail G. Lagoudakis4
1 Foundation for Research and Technology-Hellas, Institute or Applied and Computational Mathematics, Heraklion, Greece
2 University of Thessalia, Department of Orthopaedic Surgery, Medical School, Larissa, Greece3 Harvard School of Public Health, Program in Molecular and Integrative Physiological Sciences, Boston MA, USA
4 Technical University of Crete, Department of Electronic and Computer Engineering, Chania, Greece
Microenvironment Properties Dictate Cell FateMicroenvironment Properties Dictate Cell Fate
Stem cell fate is determined by
the mechanical properties of the
substrate they are exposed to. (Engler et al., Cell 126(4): 677-89, 2006)
Increased rigidity of 3D
substrates is accompanied by
switching to malignant
phenotype of mammary
epithelial cells. (Paszek et al., Cell, 74: 241-254, 2005).
Cancer cells are resilient to many physiological stresses.
Experimental QuestionsExperimental Questions
Can substrate rigidity affect cancer cell morphology?
Can substrate rigidity alter cancer cell functions?
- Apoptosis
- Mechanical output
Experimental SetupExperimental Setup
Acrylamide BIS-Acr 1kPa Brain
7 kPa Connective tissue
55 kPa Collagenous bone
Glass Control
Acrylamide BIS-Acr
Col I
Experimental SetupExperimental Setup
Heated Stage
Acrylamide BIS-Acr
Col I
Cells
Experimental SetupExperimental Setup
1 7 55 Glass0
3000
6000
9000
12000
#
*
Substrate Rigidity (kPa)
Cell Area (µµ µµm2)
1 7 55 Glass0.0
0.2
0.4
0.6
0.8
1.0
*
Substrate Rigidity (kPa)
Circularity
100 µm
11o o Human Osteosarcoma Cell Morphology and Substrate Rigidity Human Osteosarcoma Cell Morphology and Substrate Rigidity
1 7 55 Glass0
2
4
6
8
10
12*
Substrate Rigidity (kPa)
Cell Death (%)
Enhanced cell survival on rigid substratesEnhanced cell survival on rigid substrates
50 µm
Phase Apoptosis
Necrosis
Micrometers
Primary osteosarcoma cells increase traction on rigid substratesPrimary osteosarcoma cells increase traction on rigid substrates
G
R
O
Fourier Transform Traction Cytometry (Butler et al. Am J Physiol-Cell Physiol, 282: C595–C605, 2002)
Current conclusions and future workCurrent conclusions and future work
Established that substrate rigidity can impose morphological and
functional alterations to cancer cells from a cell line and primary
cells.
Investigate the molecular effectors that dictate cancer cell
mechanosensing.
Thank you for your attention!Thank you for your attention!