FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2987005877> ?p ?o ?g. }

• W2987005877 abstract "Topographical cues patterned on surfaces activate specific cell morphologies, functions and behaviours. This leads to patterned surfaces emerging as in vitro platforms to study cell behaviour and in vivo devices for tissue regeneration. Yet the current practice in the field merely screens pre-made topography libraries to obtain biological hits, providing little to no biological intuition in design and severely limiting diversity of topographies. This thesis presents an alternative methodology to topography design that exploits morphological and functional responses of cells.First, we established the relationship between nanopit topography structure, cell form and function. An image-based profile of focal adhesions, actin and chromatin were measured from single cells to create a morphological profile of cells termed the ‘morphome’. Using the morphome as predictors, 6 musculoskeletal cell types (accuracy of 98-99%) were classified using logistic regression. Meanwhile, nanopit diameter and disorder from a perfect square grid were accurately predicted (mean absolute error of 2-10%) from the morphome using linear regression. The morphome clearly reflected functional response to topography by robustly predicting (mean absolute error of 10-21%) expression levels of 14 musculoskeletal genes across 24 combinations of cell type and topography using linear regression.Next, we utilized the topography structure and cell function information encoded in the morphome to demonstrate functionally-guided topography design. A Bayesian optimisation algorithm attained maximum osteogenic gene expression and the corresponding optimum morphome, from which pit topography characteristics were predicted. Pits with hexagonal geometry, 255 nm diameter and 183 nm disorder or square geometry, 398 nm diameter and 399 nm disorder were therefore predicted to maximize osteogenic gene expression. Compared to a random approach (average of 43), topography design through optimizing cell function also reduced the number of experiments (average of 27) needed to achieve the optimum topography.Finally, we studied the mechanism through which the morphome linked topography structure and cell function. Mechanosensing and functional cell regimes were altered by a library of disordered nanopits. Nanopits with disorder of 20, 50 and 120 nm induced strong osteogenic response that correlated with formation of actin stress fibers, and assembly of large adhesions with longer lifetimes and localization of tension-related components. Cells on nanotopographies with disorder of 0 and 80 nm manifested lamellipodial protrusions containing small adhesions with high turnover, precluding the development of tension required for osteogenesis. Our results implicate intracellular tension generation as a key biological process reflected in the morphome.The work presented here furthers a rational approach to topography design using the structural and biological information encoded in the morphome. The morphome enables broader and more efficient design of biologically valuable topographies compared to the prevailing trial and error method." @default.
• W2987005877 created "2019-11-22" @default.
• W2987005877 creator A5074340015 @default.
• W2987005877 date "2019-01-01" @default.
• W2987005877 modified "2023-09-22" @default.
• W2987005877 title "Correlating single cell form and function under the influence of nanotopography" @default.
• W2987005877 hasPublicationYear "2019" @default.
• W2987005877 type Work @default.
• W2987005877 sameAs 2987005877 @default.
• W2987005877 citedByCount "0" @default.
• W2987005877 crossrefType "dissertation" @default.
• W2987005877 hasAuthorship W2987005877A5074340015 @default.
• W2987005877 hasConcept C171250308 @default.
• W2987005877 hasConcept C186060115 @default.
• W2987005877 hasConcept C192562407 @default.
• W2987005877 hasConcept C2524010 @default.
• W2987005877 hasConcept C2777803738 @default.
• W2987005877 hasConcept C33923547 @default.
• W2987005877 hasConcept C86803240 @default.
• W2987005877 hasConceptScore W2987005877C171250308 @default.
• W2987005877 hasConceptScore W2987005877C186060115 @default.
• W2987005877 hasConceptScore W2987005877C192562407 @default.
• W2987005877 hasConceptScore W2987005877C2524010 @default.
• W2987005877 hasConceptScore W2987005877C2777803738 @default.
• W2987005877 hasConceptScore W2987005877C33923547 @default.
• W2987005877 hasConceptScore W2987005877C86803240 @default.
• W2987005877 hasLocation W29870058771 @default.
• W2987005877 hasOpenAccess W2987005877 @default.
• W2987005877 hasPrimaryLocation W29870058771 @default.
• W2987005877 hasRelatedWork W1966913509 @default.
• W2987005877 hasRelatedWork W1986623338 @default.
• W2987005877 hasRelatedWork W2005583277 @default.
• W2987005877 hasRelatedWork W2037560180 @default.
• W2987005877 hasRelatedWork W2072974795 @default.
• W2987005877 hasRelatedWork W2079162389 @default.
• W2987005877 hasRelatedWork W2080392390 @default.
• W2987005877 hasRelatedWork W2163884408 @default.
• W2987005877 hasRelatedWork W2341608802 @default.
• W2987005877 hasRelatedWork W2549198633 @default.
• W2987005877 hasRelatedWork W1864770528 @default.
• W2987005877 isParatext "false" @default.
• W2987005877 isRetracted "false" @default.
• W2987005877 magId "2987005877" @default.
• W2987005877 workType "dissertation" @default.