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UID:1007@bioscience.fi
DTSTART;TZID=Europe/Helsinki:20240412T120000
DTEND;TZID=Europe/Helsinki:20240412T150000
DTSTAMP:20250304T083756Z
URL:https://bioscience.fi/events/dissertation-defence-aleksi-isomursu/
SUMMARY:Dissertation Defence: Aleksi Isomursu
DESCRIPTION:FM Aleksi Isomursu  defended his doctoral dissertation titled 
 "Biomechanics of cancer cell motility" at the University of Turku on Frida
 y\, April 12\, 2024\n\nThe opponent was Professor Adam J. Engler (Universi
 ty of California\, United States)\, and the custos Professor Johanna Ivask
 a (University of Turku).\n\nSummary of the Dissertation\n\nMetastatic canc
 er is a devastating disease and an unmet clinical need. The local invasion
  and colonization of distant organs by cancer cells are both dependent on 
 cell migration\, a conserved cellular process that allows eukaryotic cells
  to traverse complex tissue microenvironments. This is achieved by dynamic
  regulation of the intracellular cytoskeleton and varying degrees of adhes
 ion between cells and the extracellular milieu. Integrins are dimeric tran
 smembrane receptors and the main cell adhesion molecules responsible for m
 ediating interactions between cells and the extracellular matrix (ECM). Th
 ey transmit cytoskeletal forces to the ECM\, facilitating cell migration a
 nd ECM remodeling\, and simultaneously inform the cell of the molecular co
 mposition and biomechanical properties of the local microenvironment. Mali
 gnant tumors are characterized by aberrant ECM architecture and other phys
 ical traits that differ markedly from healthy tissues. Tissue biomechanics
  can influence most cellular processes\, including migration\, but many of
  the underlying mechanisms are still inadequately understood.\n\nThis thes
 is provides new insights into the direct and indirect mechanisms that cont
 ribute to the biomechanical regulation of cancer cell motility. New tools 
 for preparing cell culture substrates with stiffness gradients or dynamic 
 micropatterns were established and used to investigate mechanically direct
 ed cell migration\, cell polarization in response to local ECM geometry\, 
 and mechanosensitivity of ECM-remodeling adhesions. We found that the grow
 th of fibrillar adhesions (FB)\, integrin adhesion complexes (IAC) respons
 ible for fibronectin fibrillogenesis\, is directly responsive to substrate
  stiffness. Further\, we observed for the first time that human glioblasto
 ma cells can migrate preferentially toward more compliant environments. Th
 is behavior\, and the conventional positive durotaxis in other adherent ce
 lls\, was explained by the molecular clutch model of cell adhesion. Finall
 y\, we found that cell front-rear polarization on anisotropic micropattern
 s is dependent on the biochemical composition of the substrate\, impacting
  migration when the cells are released on fibronectin. Taken together\, th
 e results presented here improve our understanding of the different biomec
 hanical cues that regulate and guide the movement of human cells. They als
 o provide technological advancements for studying various aspects of cance
 r mechanobiology.\n\nDownload dissertation
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