we herd living cells like sheep using
biomaterial- and bioelectric sheepdogs

The Work

Cells in tissues behave as communities with similarities to flocks of birds, human cities, and herds of sheep. This means that many of the tools we use to engineer communities, from urban planning to sheep herding can be applied to living tissues! 

In the Cohen Lab, we study these cellular collective and communal behaviors to better: (1) understand; (2) heal; and (3) grow tissues.

In particular, we build bioelectric sheepdogs and
materials that mimic cells, and we study the
social lives of cells within tissues.

The Crew

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Daniel Cohen

Group Leader and Cell-Herder-In-Chief; CV Here

Kevin

Kevin Suh

Does physics to cells

Elena

Elena Cho

Makes cell costumes

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Celeste Rodriguez

Ask me later

Senior Graduate Student

Gawoon Shim

Cells fear her

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Irving Miramontes

Looks deep inside cells

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This could be you

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Lisset Rosario

Waterbear wrangler

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Avi Wolf

Cells and gels

Isaac

Isaac Breinyn

Barks at cells

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Dr. Anamika Singh

Biomaterials and Stem Cells

Graduate and Post-doc Survivors

  • Dr. Matthew Heinrich (Moderna)
  • Dr. Julienne LaChance (Sony AI)
  • Dr. Tom Zajdel (Faculty, Carnegie-Mellon)

The Papers

Wolf A, Heinrich MA*, Breinyn I*, Zajdel TJ,and Cohen DJ. Short-term stimulation of collective cell migration induces long-term, supracellular changes to tissue behavior, PNAS Nexus (2022)

  • We've done a lot of work to show how bioelectric cues can be used to literally steer cells in tissues around for healing and growth control, but a hole in the field has been understanding how different members within a group respond to the same field, and how well they remember having been electrically stimulated even after the electrical cue is turned off. Here, we showed that the same electrical stimulus applied to a whole tissue can lead to cells doing different things depending on where they are within a tissue! We also proved that tissues remember having been stimulated for many hours after even a short period of electrical stimulation. These concepts will help us to better optimize and design next-gen bioelectric tools. 

Shim G, Devenport DD, and Cohen DJOverriding endogenous coordination makes cell migration more susceptible to external control,  PNAS  (2021)

  • We've been working on using bioelectric signals that mimic those that naturally occur in the body to help accelerate tissue growth and injury healing. However, we found a unique complication arises when the natural behaviors of a tissue conflict with our bioelectric command. In these cases, we found that combining bioelectricity with drugs that gently disrupt 'cell handholding' makes cells obey our commands more effectively, allowing us to accelerate model skin healing. 

Nirody J, Rosario LD, Johnston D, and Cohen DJTardigrades exhibit robust interlimb coordination across walking speeds, PNAS  (2021)

  • Waterbears may be the smallest animal with legs (8 legs total!), which makes them a really important example of what is possible at such a tiny scale (1.5X human hair thickness). We found that waterbears use a variety of clever tricks to walk at the microscale, and we also found that they use a very simple, but powerful, neural control pattern to program their 8 legs. This could help understand both the evolution of walking and the design of microscale walking robots. 

Zajdel TJ, Shim G, and Cohen DJCome together:  Bioelectric ’healing-on-a-chip’ to accelerate tissue healing, Biosensors and Bioelectronics  (2021)

  • Bioelectric fields pop up immediately upon receiving a skin injury. These signals act like navigational cues that help activate healing processes and tell cells where to go during healing. We built a device that mimics the shape of these fields, but amplifies the electric field strength to accelerate healing and tested it in simple skin layers cultured in a Petri dish. 

Hart KC, Sim JY, Hopcroft MA, Cohen DJ, Tan J, Nelson WJ, and Pruitt BL. An Easy-to-Fabricate Cell Stretcher Reveals Density-Dependent Mechanical Regulation of Collective Cell Movements in Epithelia, Cellular and Molecular Bioengineering (2021)

  • We helped to analyze how a 3D-printable cell stretching device applies mechanical strain to living tissues and how the induced strain drives changes to collective cell migration. 

Zajdel, TJ., Shim G, Wang L, Rossello M, and Cohen DJSCHEEPDOG: Programming Electric Cues to Herd Cell Migration, Cell Systems (2020)

  • Bioelectric signals permeate the body, entirely separate from the nervous system! These signals come from ionic currents and play an important role in telling cells where to move. We built a multi-electrode system that hacks these natural fields and allows us to completely program cellular motion in 2D, kind of like a cellular 'etch-a-sketch'! This approach can be useful for tissue engineering and healing injuries. 

Heinrich MA, Alert R, LaChance J, Zajdel TJ, Kosmrlj A, and Cohen DJ. Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia, eLife (2020)

  • For a tissue to change shape or grow during development or healing requires thousands of cells to decide whether to move or divide to make new cells. This coordination is quite complicated and and we demonstrate here how the size of a tissue can lead to unique behavioral 'zones' across the tissue that affect growth and healing. 

Bisaria A, Hayer A, Garbett D, Cohen DJ, and Meyer T. Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration, Science (2020)

  • We collaborated with the Meyer Lab here to make single cell-wide 'highways' that make it much easier to study subcellular, migratory dynamics since the cells can only move forward or backwards. These tools helped to reveal how spatiotemporal activation of molecular motors can organize cell migraton. 

LaChance JM and Cohen DJ. Practical Fluorescence Reconstruction Microscopy for Large Samples and Low-Magnification Imaging, PLoS Comp. Bio. (2020)

  • While fluorescence microscopy is very powerful, the act of observing cells and microorganisms using fluorescence excitation often changes their behaviors due to light-induced toxicity and chemistry. There is also a trade-off between seeing more of a sample (lower magnification) and high-quality fluoresence imaging. Here, we used machine learning approaches to take non-toxic, gentle transmitted light images (non-fluorescent) and predict what the equivalent fluorescent images would look like for many common cell markers. Give it a shot! 

Cohen DJ, Nelson WJ. Secret Handshakes: cell-cell recognition and adhesion, Current Opinion in Cell Biology (2018)

Cohen DJ, Gloerich M, Nelson WJ. Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction, PNAS (2016)

Gloerich M, Bianchini JM, Siemers KA, Cohen DJ, Nelson WJ. Cell division orientation is coupled to cell- celladhesion by the E-cadherin/LGN complex, Nature Communications (2016)

Cohen DJ, Nelson WJ, Maharbiz MM. Galvanotactic control of collective cell migration in epithelialmonolayers, Nature Materials (2014)

Cohen DJ, Mitra D, Peterson K, Maharbiz MM. A highly elastic, capacitive strain gauge based onpercolating nanotube networks, Nano Letters (2012)

Libby T, Moore TY, Chang-Siu E, Li D, Cohen DJ, Jusufi A, Full RJ. Tail-assisted pitch control in lizards, robots and dinosaurs, Nature (2012)

Chen J, Bly RA, Saad MM, Alkhodary MA, El-Backly RM, Cohen DJ, Kattamis N, Fatta MM, Moore WA, Arnold CB, Marei MK, Soboyejo WO. In-vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs, Materials Science and Engineering: C (2011)

Cohen DJ, Morfino R, Maharbiz M, A Modified Consumer Inkjet for Spatiotemporal Control of GeneExpression, PLoS ONE (2009)

Pre-prints

Heinrich MA, Alert R, Wolf A, Kosmrlj A,and Cohen DJ. Self-assembly of tessellated tissue sheets by growth and collision, In Press: Nature Communications (2022); avail. bioRxiv (2021)

LaChance JM, Suh K, Clausen J, and Cohen DJ. Learning rules of collective cell migration using deep attention networks. In Press: PLoS Comp Bio (2022); Avail. bioRxiv (2021)

The News

2022: Esme *Moose* Rodal Cohen is born--development of website and social media enters a glacial phase :-). 

04/22: Graduate Student Isaac Breinyn wins an NSF GRFP award. Congrats, Isaac!

03/22: Graduate student Celeste Rodgriguez of MOL joins the lab. Welcome!

Pre 01/2022: Lots of important things happened but we need to update this 🙂

The Positions

Graduate Students: We are recruiting for the 2023/2024 academic year. All backgrounds are considered. Current project areas include bioelectronic control of tissue growth and healing; bioelectrochemical material design, cell-mimetic biomaterials; and collective cell behaviors. Please contact the PI directly for further information danielcohen<at>princeton<dot>edu

Post-doctoral fellows: We are looking for 1-2 post-doctoral fellows to join NIH and NSF funded research projects. Project areas are flexible but specific needs are in the areas of bioelectricity and bioelectronic tissue engineerings and biomaterial synthesis and testing.

Please contact the PI directly at danielcohen<at>princeton<dot>edu for specific details. Be sure to include a CV and specific description of your research interests and why you are specifically interested in our group. Inquiries without these materials will not be considered.