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Collective Behaviors in Exogenously Controlled Epithelia
Collective Behaviors in Exogenously Controlled Epithelia
Collective Behaviors in Exogenously Controlled Epithelia

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103514
ISBN  
9798280748415
DDC  
574.191
저자명  
Breinyn, Isaac B.
서명/저자  
Collective Behaviors in Exogenously Controlled Epithelia
발행사항  
[Sl] : Princeton University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
116 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Cohen, Daniel J.
학위논문주기  
Thesis (Ph.D.)--Princeton University, 2025.
초록/해제  
요약Mammalian cells leverage collective behaviors to coordinate movement, force production, and fluid pumping during a range of crucial biological processes. These collective behaviors are essential for establishing and maintaining homeostasis and require constitutive cells to accurately sense and respond to their environment. Whereas these collective behaviors are relatively well-studied in the context of confined and freely migrating mature epithelia, it remains poorly understood how they are modulated by exogenous cues. The work presented in this dissertation addresses this gap in knowledge by directly measuring collective behaviors in exogenously controlled epithelial tissues. First, we present data showing that short-term bioelectric stimulation of an epithelium has longlasting effects on collective migration in the system. We explore the spatiotemporal dynamics of migrational speed, alignment, and correlation in distinct regions of the tissue before, during, and after bioelectric stimulation. These data show that epithelia exhibit an inhomogeneous response to a homogeneous cue. We then show that bioelectric stimulation can be used in a 3D context to control fluid pumping and migration in a lab-grown kidney model via a process we call 'electro-inflation'. We performed inhibition assays and developed a continuum model to show that electro-inflation is driven by ion crowding and mediated by a balance between ion channel activity and cytoskeletal mechanics. We then generalize our study of collective behavior to exogenous cues outside of bioelectricity by presenting a bioengineered system wherein cells are forced to adhere to their substrate via cadherins - a family of proteins used exclusively in cell-cell junctions. We show that this bio-inspired functionalized system directly modulates force propagation, migrational state, and cell-cycling in the epithelium. Finally, we present ongoing work on mapping the spatiotemporal expenditure of mechanical energy in epithelia using a combination of traction force microscopy and modeling. We show that energy expenditure in epithelia is spatiotemporally patterned, scales with tissue size, and actively regulates migration. Broadly, this dissertation presents a suite of analytical and experimental methods for studying epithelial collective behavior in perturbed environments and data that may prove useful for translating bioengineering techniques such as bioelectric stimulation and surface functionalization to medical instrumentation.
일반주제명  
Biophysics
일반주제명  
Biomechanics
일반주제명  
Bioengineering
일반주제명  
Cellular biology
키워드  
Mammalian cells
키워드  
Collective behaviors
키워드  
Exogenously controlled epithelial tissues
키워드  
Fluid pumping
기타저자  
Princeton University Quantitative Computational Biology
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aBreinyn,  Isaac  B.▼0(orcid)0000-0002-4831-8398
■24510▼aCollective  Behaviors  in  Exogenously  Controlled  Epithelia
■260    ▼a[Sl]▼bPrinceton  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a116  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Cohen,  Daniel  J.
■5021  ▼aThesis  (Ph.D.)--Princeton  University,  2025.
■520    ▼aMammalian  cells  leverage  collective  behaviors  to  coordinate  movement,  force  production,  and  fluid  pumping  during  a  range  of  crucial  biological  processes.  These  collective  behaviors  are  essential  for  establishing  and  maintaining  homeostasis  and  require  constitutive  cells  to  accurately  sense  and  respond  to  their  environment.  Whereas  these  collective  behaviors  are  relatively  well-studied  in  the  context  of  confined  and  freely  migrating  mature  epithelia,  it  remains  poorly  understood  how  they  are  modulated  by  exogenous  cues.  The  work  presented  in  this  dissertation  addresses  this  gap  in  knowledge  by  directly  measuring  collective  behaviors  in  exogenously  controlled  epithelial  tissues.  First,  we  present  data  showing  that  short-term  bioelectric  stimulation  of  an  epithelium  has  longlasting  effects  on  collective  migration  in  the  system.  We  explore  the  spatiotemporal  dynamics  of  migrational  speed,  alignment,  and  correlation  in  distinct  regions  of  the  tissue  before,  during,  and  after  bioelectric  stimulation.  These  data  show  that  epithelia  exhibit  an  inhomogeneous  response  to  a  homogeneous  cue.  We  then  show  that  bioelectric  stimulation  can  be  used  in  a  3D  context  to  control  fluid  pumping  and  migration  in  a  lab-grown  kidney  model  via  a  process  we  call  'electro-inflation'.  We  performed  inhibition  assays  and  developed  a  continuum  model  to  show  that  electro-inflation  is  driven  by  ion  crowding  and  mediated  by  a  balance  between  ion  channel  activity  and  cytoskeletal  mechanics.  We  then  generalize  our  study  of  collective  behavior  to  exogenous  cues  outside  of  bioelectricity  by  presenting  a  bioengineered  system  wherein  cells  are  forced  to  adhere  to  their  substrate  via  cadherins  -  a  family  of  proteins  used  exclusively  in  cell-cell  junctions.  We  show  that  this  bio-inspired  functionalized  system  directly  modulates  force  propagation,  migrational  state,  and  cell-cycling  in  the  epithelium.  Finally,  we  present  ongoing  work  on  mapping  the  spatiotemporal  expenditure  of  mechanical  energy  in  epithelia  using  a  combination  of  traction  force  microscopy  and  modeling.  We  show  that  energy  expenditure  in  epithelia  is  spatiotemporally  patterned,  scales  with  tissue  size,  and  actively  regulates  migration.  Broadly,  this  dissertation  presents  a  suite  of  analytical  and  experimental  methods  for  studying  epithelial  collective  behavior  in  perturbed  environments  and  data  that  may  prove  useful  for  translating  bioengineering  techniques  such  as  bioelectric  stimulation  and  surface  functionalization  to  medical  instrumentation.
■590    ▼aSchool  code:  0181.
■650  4▼aBiophysics
■650  4▼aBiomechanics
■650  4▼aBioengineering
■650  4▼aCellular  biology
■653    ▼aMammalian  cells
■653    ▼aCollective  behaviors
■653    ▼aExogenously  controlled  epithelial  tissues
■653    ▼aFluid  pumping
■690    ▼a0786
■690    ▼a0648
■690    ▼a0202
■690    ▼a0379
■71020▼aPrinceton  University▼bQuantitative  Computational  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0181
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357454▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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