Multicellular architecture of malignant breast epithelia influences mechanics.
Cell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4128597?pdf=render |
| _version_ | 1818511411938066432 |
|---|---|
| author | Gautham Venugopalan David B Camarillo Kevin D Webster Clay D Reber James A Sethian Valerie M Weaver Daniel A Fletcher Hana El-Samad Chris H Rycroft |
| author_facet | Gautham Venugopalan David B Camarillo Kevin D Webster Clay D Reber James A Sethian Valerie M Weaver Daniel A Fletcher Hana El-Samad Chris H Rycroft |
| author_sort | Gautham Venugopalan |
| collection | DOAJ |
| description | Cell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the "perceived stiffness" of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing. |
| first_indexed | 2024-12-10T23:33:03Z |
| format | Article |
| id | doaj.art-abe99c7eb82d41b08f12be8f6cc7e5b7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:33:03Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-abe99c7eb82d41b08f12be8f6cc7e5b72022-12-22T01:29:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10195510.1371/journal.pone.0101955Multicellular architecture of malignant breast epithelia influences mechanics.Gautham VenugopalanDavid B CamarilloKevin D WebsterClay D ReberJames A SethianValerie M WeaverDaniel A FletcherHana El-SamadChris H RycroftCell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the "perceived stiffness" of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing.http://europepmc.org/articles/PMC4128597?pdf=render |
| spellingShingle | Gautham Venugopalan David B Camarillo Kevin D Webster Clay D Reber James A Sethian Valerie M Weaver Daniel A Fletcher Hana El-Samad Chris H Rycroft Multicellular architecture of malignant breast epithelia influences mechanics. PLoS ONE |
| title | Multicellular architecture of malignant breast epithelia influences mechanics. |
| title_full | Multicellular architecture of malignant breast epithelia influences mechanics. |
| title_fullStr | Multicellular architecture of malignant breast epithelia influences mechanics. |
| title_full_unstemmed | Multicellular architecture of malignant breast epithelia influences mechanics. |
| title_short | Multicellular architecture of malignant breast epithelia influences mechanics. |
| title_sort | multicellular architecture of malignant breast epithelia influences mechanics |
| url | http://europepmc.org/articles/PMC4128597?pdf=render |
| work_keys_str_mv | AT gauthamvenugopalan multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT davidbcamarillo multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT kevindwebster multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT claydreber multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT jamesasethian multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT valeriemweaver multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT danielafletcher multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT hanaelsamad multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics AT chrishrycroft multicellulararchitectureofmalignantbreastepitheliainfluencesmechanics |