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DTSTART:20180325T030000
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DTSTART:20181028T020000
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DTSTAMP:20260404T082459Z
UID:5b5af043bfa6c554734932@ist.ac.at
DTSTART:20180813T140000
DTEND:20180813T150000
DESCRIPTION:Speaker: Alex Lomakin\nhosted by Michael Sixt\nAbstract: Much l
 ike modern day engineered devices\, cells in the human body are able to ma
 ke precise measurements: intestinal epithelial cells monitor local cell de
 nsities to prevent hyperplasia\, neutrophils sample their microenvironment
  to compute the fastest migratory route toward infection sites\, and epide
 rmal stem cells use extracellular matrix occupancy to make cell fate decis
 ions. What these examples illustrate is the sensitivity of complex cell be
 haviors to spatial and mechanical constraints\, known in quantitative scie
 nces as boundary conditions. Although the importance of boundary condition
 s in cell and tissue physiology is increasingly recognized\, it remains un
 clear how cells sample their boundaries to tailor specific behaviors to bo
 undary conditions. Here\, using biophysical tools to manipulate cell bound
 aries in a highly controlled\, quantitative manner\, we found that cells e
 stimate externally-imposed confinement using their largest and stiffest in
 tracellular component\, the nucleus. Cell confinement below a certain thre
 shold deforms the nucleus and expands its envelope area. Unbuffered agains
 t area expansion due to slow turnover of constituents\, the nuclear envelo
 pe becomes stretched. This in turn engages signaling via nuclear membrane 
 stretch-sensitive proteins to the actomyosin cortex\, activating contracti
 lity. The latter provides a motive force for the cell to squeeze through t
 ight pores and constrictions in the extracellular matrix. Interestingly\, 
 no increase in cell contractility is observed when cells move through envi
 ronmental confines that do not significantly deform the nucleus. Thus\, th
 e nucleus acts as an internal ruler for environmental confinement size\, a
 llowing cells to utilize energetically costly contractility on demand\, on
 ly when surrounding space becomes restrictive. The advantage of the propos
 ed mechanism is that in contrast to the plasma membrane\, nuclear membrane
 s do not participate in constitutive membrane trafficking\; their surface 
 area thus fluctuates less. This intrinsic quiescence should privilege them
  to function as low-noise detectors\, to readily discriminate local enviro
 nmental conditions from internal traffic-induced cell area/tension fluctua
 tions.
LOCATION:Mondi Seminar Room 2\, Central Building\, ISTA
ORGANIZER:amally@ist.ac.at
SUMMARY:Alex Lomakin: How do cells measure their boundaries to tailor physi
 ological responses?
URL:https://talks-calendar.ista.ac.at/events/1342
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