Foundational materials

Reading and Writing the Morphogenetic Code
Foundational White Paper of the Allen Discovery Center at Tufts University


Life, death, and self: Fundamental questions of primitive cognition viewed through the lens of body plasticity and synthetic organisms
Levin, M.
Biochemical and Biophysical Research Communications, in press

Machine Learning-Driven Bioelectronics for Closed-Loop Control of Cells
Selberg, J., Jafari, M., Mathews, J., Jia, M., Pansodtee, P., Dechiraju, H., Wu, C., Cordero, S., Flora, A., Yonas, N., Jannetty, S., Diberardinis, M., Teodorescu, M., Levin, M., Gomez, M., and Rolandi, M.
Advanced Intelligent Systems, 2000140

Shape changing robots: bioinspiration, simulation, and physical realization
Shah, D., Yang, B., Kriegman, S., Levin, M., Bongard, J., and Kramer-Bottiglio, R.
Advanced Materials, in press

Does evolution have a target morphology?
Fields, C., and Levin, M.
Organisms, 4(1): 57-76

Bioelectronic Control of Chloride Ions and Concentration with Ag/AgCl Contacts
Jia, M., Dechiruji, H., Selberg J., Pansodtee P., Mathews, J., Wu, C., Levin, M., Teodorescu, M., and Rolandi, M.
APL Materials, 8(9): 091106

How Groups of Cells Cooperate to Build Organs and Organisms
Levin, M.
The Scientist

Nervous System and Tissue Polarity Dynamically Adapt to New Morphologies in Planaria
Bischof, J., Day, M., Miller, K., LaPalme, J., and Levin, M.
Developmental Biology, in press

Emergence of Informative Higher Scales in Biological Systems: a computational toolkit for optimal prediction and control
Hoel, E., and Levin, M.
Communicative & Integrative Biology, in press

Applications and ethics of computer-designed organisms
Levin, M., Bongard, J., and Lunshof, J.E.
Nature Reviews Molecular Cell Biology, in press

Bistability of Somatic Pattern Memories: Stochastic Outcomes in Bioelectric Circuits Underlying Regeneration
Pezzulo, G., Lapalme, J., Durant, F., and Levin, M.
Philosophical Proceedings of the Royal Society B, in press

Opinion: Use the Pandemic to Expand the Lab to the Home
Levin, M.
The Scientist

Regulation of axial and head patterning during planarian regeneration by a commensal bacterium
Williams, K., Bischof, J., Lee, F., Miller, K., LaPalme, J., Wolfe, B., and Levin, M.
Mechanisms of Development, 163:103614 [cover]

Competitive and Coordinative Interactions between Body Parts Produce Adaptive Developmental Outcomes
Gawne, R., McKenna, K., and Levin, M.
BioEssays, 2020: 1900245

HCN2 Channel-induced Rescue of Brain Teratogenesis via local and long-range bioelectric repair
Pai, V., Cervera, J., Mafe, S., Willocq, V., Lederer, E., and Levin, M.
Frontiers in Cellular Neuroscience, 14: 136

Bioelectrical Coupling of Single-Cell States in Multicellular Systems
Cervera, J., Levin, M., Mafe, S.
J. Phys. Chem. Lett., 11, XXX, 3234-3241,

von Willebrand factor D and EGF domains is an evolutionarily conserved and required feature of blastemas capable of multitissue appendage regeneration
Leigh, N. D., Sessa, S., Dragalzew, A. C., Payzin‐Dogru, D., Sousa, J. F., Aggouras, A. N., Johnson, K., Dunlap, G. S., Haas, B. J., Levin, M., Schneider, I., Whited, J. L.
Evolution & Development, 1–15

Sertraline induces DNA damage and cellular toxicity in Drosophila that can be ameliorated by antioxidants
Jajoo, A., Donlon, C., Shnayder, S., Levin, M., and McVey, M.
Scientific Reports, 10: 4512

Revisiting Burr and Northrop’s ‘The Electro-Dynamic Theory of Life’
Levin, M.
Biological Theory, in press

Eya2 promotes cell cycle progression by regulating DNA damage response during vertebrate limb regeneration
Sousounis, K., Bryant, D. M., Fernandez, J. M., Eddy, S. S., Tsai, S. L., Gundberg, G. C., Han, J., Courtemanche, K., Levin, M., and Whited, J. L.
eLIFE, 9:e51217

Does regeneration recapitulate phylogeny?
Fields, C., and Levin, M.
Communicative and Integrative Biology, 13(1): 27-38

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity
Herrera-Rincon, C., Pare, J-F., Martyniuk, C. J., Jannetty, S. K., Harrison C., Fischer, A., Dinis, A., Keshari, V., Novak, R., and Levin, M.
NPJ Regenerative Medicine, 5:2

A Meta-Analysis of Bioelectric Data in Cancer, Embryogenesis, and Regeneration
Srivastava, P., Kane, A., Harrison, C., and Levin, M.
Bioelectricity, in press

Toward Decoding Bioelectric Events in Xenopus Embryogenesis: New Methodology for Tracking Interplay Between Calcium and Resting Potentials In Vivo
McMillen, P., Novak, R., and Levin, M.
Journal of Molecular Biology, 432: 605-620

Optogenetically induced cellular habituation in non-neuronal cells
Bonzanni, M., Rouleau, N., Levin, M., and Kaplan, D. L.
PLOS One, 15(1):e0227230

Extra-genomic instructive influences in morphogenesis: A review of external signals that regulate growth and form
Tung, A., and Levin, M.
Developmental Biology, 461: 1-12

A scalable pipeline for designing reconfigurable organisms
Kriegman, S., Blackiston, D., Levin, M., and Bongard, J.
Proceedings of the National Academy of Sciences of the United States, doi/10.1073/pnas.1910837117

Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials
Kamaldinov, T., Erndt-Marino, J., Levin, M., Kaplan, D. L., and Hahn, M. S.
Bioelectricity, 2(1): 21-32

The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation
Levin, M.
BioEssays, 42: 1900146

Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions
Cervera, J., Meseguer, S., Levin, M., and Mafe, S.
Bioelectrochemistry, 132: 107410

Morphological Coordination: A Common Ancestral Function Unifying Neural and Non-Neural Signaling
Fields, C., Bischof, J., and Levin, M.
Physiology, 35: 16-30


Planarian Regeneration as a Model of Anatomical Homeostasis: Recent Progress in Biophysical and Computational Approaches
Levin, M., Pietak, A. M., Bischof, J.
Seminars in Cell and Developmental Biology, 87: 125-144

Membrane potential depolarization alters calcium flux and phosphate signaling during osteogenic differentiation of human mesenchymal stem cells
Sundelacruz, S., Levin, M., and Kaplan, D.
Bioelectricity, 1(1): 56-66

Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential
Bonzanni, M., Payne, S. L., Adelfio, M., Kaplan, D. L., Levin, M., and Oudin, M. J.
Biology Open, 9(1): bio048553

Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine
Levin, M., Selberg, S., and Rolandi, M.
iScience, 22: 519–533

Modeling somatic computation with non-neural bioelectric networks
Manicka, S., and Levin, M.
Scientific Reports, 9: 18612, doi:10.1038/s41598-019-54859-8

Regenerative Adaptation To Electrochemical Perturbation In Planaria: A Molecular Analysis Of Physiological Plasticity
Emmons-Bell, M., Durant, F., Tung, A., Pietak, A., Miller, K., Kane, A., Martyniuk, C. J., Davidian, D., Morokuma, J., and Levin, M.
iScience, 22: 147-165

Interdisciplinary Approach Needed to Crack Morphogenesis
Finkelstein J., McLaughlin K., Levin M.
The Scientist, December 2019

The Computational Boundary of a “Self”: developmental bioelectricity drives multicellularity and scale-free cognition
Levin, M.
Frontiers in Psychology, 10:2688, doi: 10.3389/fpsyg.2019.02688

L-type voltage-gated Ca2+ channel CaV1.2 regulates chondrogenesis during limb development
Atsuta, Y., Tomizwa, R. R., Levin, M., and Tabin, C. J.
PNAS, 116(43): 21592-21601

Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation
Grasman, J., Williams, M., Razis, C., Bonzanni, M., Golding, A., Cairns, D. M., Levin, M., and Kaplan, D. L.
ACS Biomater. Sci. Eng., 5(10): 5327-5336

Bioelectric control of metastasis in solid tumors
Payne, S. L., Levin, M., and Oudin, M. J.
Bioelectricity, 1(3): 114-130

Bioelectrical controls of morphogenesis: from ancient mechanisms of cell coordination to biomedical opportunities
Whited, J., and Levin, M.
Current Opinion in Genetics & Development, 57: 61-69 [cover]

From non-excitable single-cell to multicellular bioelectrical states supported by ion channels and gap junction proteins: electrical potentials as distributed controllers
Cervera, C., Pai, V. P., Levin, M., and Mafe, S.
Progress in Biophysics and Molecular Biology, 149: 39-53

Morphogenesis as Bayesian Inference: a Variational Approach to Pattern Formation and Control in Complex Biological Systems
Kuchling, F., Friston, K., Georgiev, G., and Levin, M.
Physics of Life Reviews, in press

Mechanisms of physiological tissue remodeling in animals: Manipulating tissue, organ, and organism morphology
Pinet K, McLaughlin KA.
Dev Biol., 2019 Apr 8. pii: S0012-1606(18)30759-0. doi: 10.1016/j.ydbio.2019.04.001 [cover]

Recovery of the Xenopus laevis heart from ROS-induced stress utilizes conserved pathways of cardiac regeneration
Jewhurst K, McLaughlin KA. Dev Growth Differ., 2019 Apr;61(3):212-227. doi: 10.1111/dgd.12602

Synchronization of Bioelectric Oscillations in Networks of Nonexcitable Cells: From Single-Cell to Multicellular States
Cervera, J., Manzanares, J. A., Mafe, S., and Levin, M.
Journal of Physical Chemistry B, 123: 3924-3934 [cover]

The Cognitive Lens: a primer on conceptual tools for analysing information processing in developmental and regenerative morphogenesis
Manicka, S., and Levin, M.
Phil. Trans. R. Soc. B, 374: 20180369

Neural control of body-plan axis in regenerating planaria
Pietak, A., Bischof, J., LaPalme, J., Morokuma, J., and Levin, M.
PLOS Computational Biology, 15(4): e1006904

A Call for a Better Understanding of Causation in Cell Biology
Bizzari, M., Brash, D., Briscoe, J., Grieneisen, V., Stern, C. D., and Levin, M.
Nature Reviews Molecular Cell Biology, 20(5): 261-262

Toward modeling regeneration via adaptable echo state networks
Hammelman, J., Siegelmann, H., Manicka, S., and Levin, M., in A. Adamatzky, S. Akl, and G. Sirakoulis (Eds.), From parallel to emergent computing, Chapter 6, pages 117-133, CRC Press

Effects of ivermectin exposure on regeneration of D. dorotocephala planaria: exploiting human-approved ion channel drugs as morphoceuticals
Ferenc, N. N., and Levin, M.
Macromolecular Bioscience, 19(3): 1800237 [cover]


EDEn – Electroceutical Design Environment: An Ion Channel Database with Small Molecule Modulators and Tissue Expression Information
Churchill, C. D. M., Winter, P., Tuszynski, J. A., and Levin, M.
iScience, 11: 42-56

The bacterial metabolite indole inhibits regeneration of the planarian flatwork Dugesia japonica
Lee, F. J., Williams, K. B., Levin, M., and Wolfe, B. E.
iScience, 10: 135-148

Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb
Herrera-Rincon, C., Golding, A. S., Moran, Harrison, C., Martyniuk, C. J., Guay, J. A., Zaltsman, J., Carabello, H., Kaplan, D. L., and Levin, M.
Cell Reports, 25: 1593-1609

Entropic effects in cell lineage tree packings
Jasmin Imran Alsous, Paul Villoutreix, Norbert Stoop, Stanislav Y. Shvartsman & Jörn Dunkel
Nature Physics, 14: 1016–1021 [cover]

Ivermectin promotes peripheral nerve regeneration during wound healing
Cairns, D. M., Giordano, J. E., Conte, S., Levin, M., and Kaplan, D. L.
ACS Omega, 3: 12392-12402

Activating PAX gene family paralogs to complement PAX5 leukemia driver mutations
Hart, M. R., Anderson, D. J., Porter, C. C., Neff, T., Levin, M., Horwitz, M. S.
PLoS Genetics, 4(9): e1007642

Cross-limb Communication During Xenopus Hind-limb Regenerative Response: Non-Local Bioelectric Injury Signals
Busse, S. M., McMillen, P. T., and Levin, M.
Development,145(19). pii: dev164210. doi: 10.1242/dev.164210

Inform: Efficient Information-Theoretic Analysis of Collective Behaviors
Moore, D. G., Valentini, G., Walker, S. I., and Michael Levin
Frontiers in Robotics and AI, 5: 60

Bioelectrical coupling in multicellular domains regulated by gap junctions: a conceptual approach
Cervera, J., Pietak, A., Levin, M., and Mafe, S.
Bioelectrochemistry 2018;123: 45-61 [cover]

Bioelectrical control of positional information in development and regeneration: a review of conceptual and computational advances
Alexis Pietak and Michael Levin
Progress in Biophysics and Molecular Biology 137: 52-68

The Body Electric 2.0: Recent Advances in Developmental Bioelectricity for Regenerative and Synthetic Bioengineering
Juanita Mathews and Michael Levin
Curr Opin Biotechnol. 52: 134-144

Are planaria individuals? What regenerative biology is telling us about the nature of multicellularity
Fields C, Levin M
Evolutionary Biology. 2018;45:237–247. doi: 10.1007/s11692-018-9448-9

Embodying Markov blankets: Comment on “Answering Schrödinger’s question: A free-energy formulation” by Maxwell James Désormeau Ramstead et al.
Pezzulo G, Levin M
Phys Life Rev. 2018 Mar;24:32-36. doi: 10.1016/j.plrev.2017.11.020

Multiscale memory and bioelectric error correction in the cytoplasm-cytoskeleton-membrane system
Fields C, Levin M
Wiley Interdiscip Rev Syst Biol Med.2018 Mar;10(2). doi: 10.1002/wsbm.1410 [cover]

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns
Pai VP, Pietak A, Willocq V, Ye B, Shi NQ, Levin M
Nat Commun. 2018 Mar 8; 9(1): 998

Inverse Drug Screening of Bioelectric Signaling and Neurotransmitter Roles: Illustrated Using a Xenopus Tail Regeneration Assay
Sullivan KG, Levin M
Cold Spring Harb Protoc. 2018 Mar 1;2018(3):pdb.prot099937. doi: 10.1101/pdb.prot099937

Booting up the organism during development: Pre-behavioral functions of the vertebrate brain in guiding body morphogenesis
Herrera-Rincon C, Levin M
Commun Integr Biol.
2018 Feb 15;11(1):e1433440. doi: 10.1080/19420889.2018.1433440 [cover]

The bioelectric code: An ancient computational medium for dynamic control of growth and form
Levin M, Martyniuk CJ
Biosystems. 2018 Feb;164:76-93. doi: 10.1016/j.biosystems.2017.08.009

Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells
Cairns DM, Boorgu DSSK, Levin M, Kaplan DL
Biol Open. 2018 Jan 29;7(1). pii: bio031807. doi: 10.1242/bio.031807

Bioelectric signaling in regeneration: Mechanisms of ionic controls of growth and form
McLaughlin KA, Levin M
Dev Biol. 2018 Jan 15;433(2):177-189. doi: 10.1016/j.ydbio.2017.08.032


Identification of regenerative roadblocks via repeat deployment of limb regeneration in axolotls
Bryant DM, Sousounis K, Payzin-Dogru D, Bryant S, Sandoval AGW, Martinez Fernandez J, Mariano R, Oshiro R, Wong AY, Leigh ND, Johnson K, Whited JL
npj Regen Med. 2017 Nov 6;2:30. doi: 10.1038/s41536-017-0034-z

HCN4 Ion Channel Function is Required for Early Events that Regulate Anatomical Left-Right Patterning in a Nodal- and Lefty-Independent Manner
Pai VP, Willocq V, Pitcairn EJ, Lemire JM, Paré JF, Shi NQ, McLaughlin KA, Levin M
Biol Open. 2017 Oct 15;6(10):1445-1457. doi: 10.1242/bio.025957

Bioelectric gene and reaction networks: computational modelling of genetic, biochemical and bioelectrical dynamics in pattern regulation
Pietak A, Levin M
J R Soc Interface. 2017 Sep;14(134). pii: 20170425. doi: 10.1098/rsif.2017.0425 [cover]

The brain is required for normal muscle and nerve patterning during early Xenopus development
Herrera-Rincon C, Pai VP, Moran KM, Lemire JM, Levin M
Nat Commun. 2017 Sep 25;8(1):587. doi: 10.1038/s41467-017-00597-2

Collective Growth in a Small Cell Network
Imran Alsous J, Villoutreix P, Berezhkovskii AM, Shvartsman SY
Curr Biol. 2017 Sep 11;27(17):2670-2676.e4. doi: 10.1016/j.cub.2017.07.038

The Zahn Drawings: New Illustrations of Xenopus Embryo and Tadpole Stages for Studies of Craniofacial Development
Zahn N, Levin M, Adams DS
Development. 2017 Aug 1;144(15):2708-2713. doi: 10.1242/dev.151308 [cover]

Endogenous Bioelectric Signaling Networks: Exploiting Voltage Gradients for Control of Growth and Form
Levin M, Pezzulo G, Finkelstein JM
Annu Rev Biomed Eng. 2017 Jun 21;19:353-387. doi: 10.1146/annurev-bioeng-071114-040647

Planarian regeneration in space: persistent anatomical, behavioral, and bacteriological changes induced by space travel
Morokuma J, Durant F, Williams KB, Finkelstein JM, Blackiston DJ, Clements T, Reed DW, Roberts M, Jain M, Kimel K, Trauger SA, Wolfe BE, Levin M
Regeneration (Oxf). 2017 Jun 13;4(2):85-102. doi: 10.1002/reg2.79 [cover]

Bioelectric regulation of innate immune system function in regenerating and intact Xenopus laevis
Paré JF, Martyniuk CJ, Levin M
npj Regen Med. 2017 May 26;2:15. doi: 10.1038/s41536-017-0019-y

Long-term, stochastic editing of regenerative anatomy via targeting endogenous bioelectric gradients
Durant F, Morokuma J, Fields C, Williams K, Adams DS, Levin M
Biophys J. 2017 May 23;112(10):2231-2243. doi: 10.1016/j.bpj.2017.04.011 [cover]

Coordinating heart morphogenesis: a novel role for Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels during cardiogenesis in Xenopus laevis
Pitcairn E, Harris H, Epiney J, Pai VP, Lemire JM, Ye B, Shi NQ, Levin M, McLaughlin KA.
Commun Integr Biol. 2017 May 10;10(3):e1309488. doi: 10.1080/19420889.2017.1309488. [cover]

Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
Tuszynski J, Tilli TM, Levin M
Curr Pharm Des. 2017;23(32):4827-4841. doi: 10.2174/1381612823666170530105837

Repeated removal of developing limb buds permanently reduces appendage size in
the highly-regenerative axolotl

Bryant DM, Sousounis K, Farkas JE, Bryant S, Thao N, Guzikowski AR, Monaghan JR, Levin M, Whited JL
Dev Biol. 2017 Apr 1;424(1):1-9. doi: 10.1016/j.ydbio.2017.02.013 [cover]

Serotonergic stimulation induces nerve growth and promotes visual learning via posterior eye grafts in a vertebrate model of induced sensory plasticity
Blackiston DJ, Vien K, Levin M.
npj Regen. Med. 2017 Mar 30; 8. doi:10.1038/s41536-017-0012-5

Reversals of bodies, brains, and behavior: quantitative analysis of laterality and its disturbance in model species,
Blackiston DJ and Levin M
in L. J. Rogers and G. Vallortigara (Eds.), Lateralized Brain Functions: Methods in Human and Non-human Species, “Neuromethods”, W. Walz (Ed.), 122: 667-694

Modeling regenerative processes with Membrane Computing
Garcia-Quismondo M, Levin M, Lobo, D
Information Sciences. 2017 381: 229-249. doi:10.1016/j.ins.2016.11.017

Discovering novel phenotypes with automatically inferred dynamic models: a partial melanocyte conversion in Xenopus
Lobo D, Lobikin M, Levin M
Sci Rep.2017 Jan 27;7:41339. doi: 10.1038/srep41339


Introduction to provocative questions in left-right asymmetry
Levin M, Klar AJ, Ramsdell AF
Philos Trans R Soc Lond B Biol Sci. 2016 Dec 19;371(1710). pii: 20150399 [cover]

From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left-right patterning
McDowell G, Rajadurai S, Levin M
Philos Trans R Soc Lond B Biol Sci. 2016 Dec 19;371(1710). pii: 20150409

Top-down models in biology: explanation and control of complex living systems
above the molecular level

Pezzulo G, Levin M
J R Soc Interface. 2016 Nov;13(124). pii: 20160555

Vertically- and horizontally-transmitted memories – the fading boundaries between regeneration and inheritance in planaria
Neuhof M, Levin M, Rechavi O
Biol Open. 2016 Sep 15;5(9):1177-88. doi: 10.1242/bio.020149 [cover]

Physiological inputs regulate species-specific anatomy during embryogenesis and

Sullivan KG, Emmons-Bell M, Levin M
Commun Integr Biol. 2016 Jul 15;9(4):e1192733. doi: 10.1080/19420889.2016.1192733

Exploring Instructive Physiological Signaling with the Bioelectric Tissue Simulation Engine
Pietak A, Levin M
Front Bioeng Biotechnol. 2016 Jul 6;4:55. doi: 10.3389/fbioe.2016.00055

A computational model of planarian regeneration
De A, Chakravarthy VS, Levin M
International Journal of Parallel, Emergent and Distributed Systems. 2016 May 24:1-7. doi:10.1080/17445760.2016.1185521

Physiological controls of large-scale patterning in planarian regeneration: a molecular and computational perspective on growth and form
Durant F, Lobo D, Hammelman J, Levin M
Regeneration (Oxf). 2016 Apr 28;3(2):78-102. doi: 10.1002/reg2.54 [cover]