Professor of Bioengineering at UCSD. Researching how cells move and metastasize in cancer and bloodstream infections.
San Diego, CA
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Cells embedded inside these synthetic hydrogels and using their own MMPs showed a similar response, spreading less in the cell-degradable (CD) gels than the non-degradable (ND) gels.
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Cells sensed these MMP-induced changes in stress relaxation, spreading less and forming fewer and smaller focal adhesions.
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To verify that cells were actually sensing the changes in stress relaxation caused by MMPs, we engineered a synthetic hydrogel with MMP-degradable peptides. When treated with increasing amounts of MMPs, its stiffness doesn't change, but it relaxes faster, like the natural ECM.
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and the mechanics of the ECM. Increasing MMPs didn't change the stiffness of the ECM, but did increase its stress relaxing behavior.
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In this study, the incredibly talented @badz_nithin asked whether the small cuts in the ECM cells make with their MMPs change the mechanics of the environment in a way that cells can feel...a feedback loop! We found that even small amounts of MMPs change the architecture...
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Cells do this in multiple ways, including by using enzymes called matrix metalloproteinases (MMPs) to trim away at their environment, the extracellular matrix (ECM).
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📢Paper alert: Matrix degradation enhances stress relaxation, regulating cell adhesion and spreading | PNAS. Often our studies focus on how the mechanics of the environment impact cell behavior...but it's a two-way street...cells can also effect changes on their environment.
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We’re looking for three new members of the SIG council, nominate someone or apply yourself here:
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A cellular Potts model (CPM) predicts these dependencies and lends new insight into how we might control collective cell migration and tissue-level structure formation. Lots of implications for #organoids and #Cancer
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However, MMP inhibition doesn't abolish matrix remodeling...instead, matrix remodeling continues but in a global pattern, localized isotropically around RCM cell clusters.
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ICM depends on localized MMP-mediated matrix remodeling. Inhibition of MMPs delocalizes MT1-MMP and switches cells to RCM.
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We found that in confining ECM, the localization and type of matrix remodeling regulates rotational versus invasive collective migration behaviors (RCM vs. ICM), which in concert with proliferation, produce acinar and duct-like structures, respectively.
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Paper alert! Ever wondered how the collective migration behaviors that form ducts and acini, the two major structural subunits of epithelial tissues, are regulated? Our findings may surprise you...
authors.elsevier.com/sd/arti…
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Please share this exciting postdoctoral research opportunity @fraleylab @ucsdbe @cancercellmap with any newly minted Ph.D.s you know who are interested in #CancerResearch and cancer-ECM interactions. #postdocjobs
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I am SO PROUD of these newly minted PhDs who are soaring out of the @FraleyLab @ucsdbe @UCSDJacobs nest. April, Will, & Sural achieved excellence in research and life despite the harrowing struggles of the last 3yrs! The future is very bright 💫
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I am so proud to congratulate the newly minted Dr. April Aralar of @FraleyLab @ucsdbe @UCSDJacobs for her excellent thesis defense today! April’s studies advanced our UdHRM technology all the way to clinical samples! Stay tuned for a tweetorial!
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I am so excited for how far Melio has taken our next-gen pathogen detection technology! Melio - IndieBio SF Demo Day 13 piped.video/7Vu9DBcqTtA via @YouTube
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Spread the word to your #SoCal #SystemsBiology friends, this will be a great in-person meeting! @UCSDJacobs @ucsdbe
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#tapsacrossamerica for those we miss dearly and appreciate beyond words
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Thank you so much, @deniswirtz ! I couldn’t have done it without your bottomless support and energy! And Greg Longmore as well (who isn’t on Twitter?) Glad to be a part of your brood!
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eLife will be visiting UCSD this Monday, May 13 in the Fung Auditorium at 11am. If you do bioscience, join us to learn more about interacting with this innovative and forward thinking journal! @UCSDnews @UCSDJacobs @ucsdbe @UCSDMedSchool
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That must have been so fun to helicopter over! We took the lift to Aguillle du Midi today and saw some other worldly skiing going on at the top.
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Congratulations Dr. Daniel Velez Ortiz on a very successful thesis defense! #phdlife #thesis #1stgradstudent @FraleyLab @bmdaort @ucsdbe @UCSDJacobs #grandgrad @deniswirtz
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UCSD students representing well at the UC-wide Bioengineering Symposium in Riverside @FraleyLab @UCSDJacobs @bmdaort
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Congrats to Dr. Mridu Sinha and Hannah Mack, who advanced our digital DNA melting platform another important step towards #precisionmedicine for neonates. Check it out in SLAS Technology: journals.sagepub.com/doi/abs…. @ucsdbe, @SLAS_org, @UCSDJacobs.
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Awesome run today @UCSanDiego for the #Triton5k with the Fraley Lab and friends! Team shirt design by the soon to be famous Sural Ranamukhaarachchi!
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Mridu wins another award for her excellent work building our digital high resolution melt platform for single cell level profiling of infectious pathogens! Well done!
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