Malcolm Steinberg

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Malcolm Saul Steinberg (June 1, 1930 - February 7, 2012) was an American biologist[https://www.princeton.edu/main/news/archive/S32/99/46E70/index.xml?section=topstories Obituary] who proposed the differential adhesion hypothesis as a mechanism explaining cell sorting during embryogenesis and cancer.{{cite journal |last1=Steinberg |first1=Malcolm S. |date=1962 |title=On the mechanism of tissue reconstruction by dissociated cells, I. Population kinetics, differential adhesiveness, and the absence of directed migration |journal=Proc Natl Acad Sci USA |volume=48 |issue=9 |pages=1577–1582 |doi=10.1073/pnas.48.9.1577 |pmid=13916689 |pmc=221002 |bibcode=1962PNAS...48.1577S |doi-access=free }}{{cite journal |last1=Steinberg |first1=Malcolm S. |date=1962 |title=Mechanism of tissue reconstruction by dissociated cells. II. Time-course of events |url=https://pubmed.ncbi.nlm.nih.gov/13916688/ |journal=Science |volume=137 |issue=3532 |pages=762–3 |doi=10.1126/science.137.3532.762 |pmid=13916688 |bibcode=1962Sci...137..762S |s2cid=29591598 |access-date=May 19, 2021}}{{cite journal |last1=Steinberg |first1=Malcolm S. |date=1963 |title=Reconstruction of tissues by dissociated cells. Some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation |url=https://pubmed.ncbi.nlm.nih.gov/13983728/ |journal=Science |volume=141 |issue=3579 |pages=401–8 |doi=10.1126/science.141.3579.401 |pmid=13983728 |access-date=May 19, 2021}}{{cite journal |last1=Steinberg |first1=Malcolm S. |date=1970 |title=Does differential adhesion govern self-assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells |url=https://pubmed.ncbi.nlm.nih.gov/5429514/ |journal=J Exp Zool |volume=173 |issue=4 |pages=395–433 |doi=10.1002/jez.1401730406 |pmid=5429514 |bibcode=1970JEZ...173..395S |access-date=May 19, 2021}}

Steinberg proposed that when cells form distinct tissues, specific cell-cell adhesion between cells from the same tissue can drive the separation. He further proposed that a difference in level of cell adhesion molecules expression between two cell types was sufficient to drive the separation.{{cite journal |last1=Steinberg |first1=Malcolm S. |date=1975 |title=Adhesion-guided multicellular assembly: a commentary upon the postulates, real and imagined, of the differential adhesion hypothesis, with special attention to computer simulations of cell sorting |url=https://pubmed.ncbi.nlm.nih.gov/1207170/ |journal=J Theor Biol |volume=55 |issue=2 |pages=431–43 |doi=10.1016/s0022-5193(75)80091-9 |pmid=1207170 |bibcode=1975JThBi..55..431S |access-date=May 19, 2021}} He confirmed these predictions in a model system in which adhesion between cells of a cultured line of mouse cells was controlled by genetic expression levels of cadherin.{{cite journal |last1=Steinberg |first1=Malcolm S. |last2=Takeichi |first2=Masatoshi |date=1994 |title=Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression |journal=Proc Natl Acad Sci USA |volume=91 |issue=1 |pages=206–9 |doi=10.1073/pnas.91.1.206 |pmid=8278366 |pmc=42915 |bibcode=1994PNAS...91..206S |doi-access=free }}

Steinberg pioneered work in characterizing the physical properties of cells and tissues. He proposed that cell-cell adhesion drives tissue rounding up and, comparing tissues to liquids, he proposed that tissues have a surface tension. To measure tissue surface tension, he participated in building a compression device for rounded cell aggregates,{{cite journal |last1=Foty |first1=Ramsey A. |last2=Pfleger |first2=Cathie M. | last3=Forgacs |first3=Gabor | last4=Steinberg |first4=Malcolm S. |date=1996 |title=Surface tensions of embryonic tissues predict their mutual envelopment behavior |url=https://pubmed.ncbi.nlm.nih.gov/8625847/ |journal=Development |volume=122 |issue=5 |pages=1611–20 |doi=10.1242/dev.122.5.1611 |pmid=8625847 |access-date=May 19, 2021}}{{cite journal |last1=Davis |first1=Grayson S. |last2=Phillips |first2=Herbert M. |last3=Steinberg |first3=Malcolm S. |date=1997 |title=Germ-layer surface tensions and "tissue affinities" in Rana pipiens gastrulae: quantitative measurements |journal=Dev Biol |volume=192 |issue=2 |pages=630–44 |doi=10.1006/dbio.1997.8741 |pmid=9441694 |doi-access=free }} and in sessile droplet experiments in which aggregates of cells were centrifuged at 37 degrees until their shapes reached equilibrium.{{cite journal |last1=Phillips |first1=Herbert M. |last2=Steinberg |first2=Malcolm S. |date=1969 |title=Equilibrium measurements of embryonic chick cell adhesiveness. I. Shape equilibrium in centrifugal fields |journal=Proc Natl Acad Sci USA |volume=64 |issue=1 |pages=1212–7 |doi=10.1073/pnas.64.1.121 |pmid=5262993 |pmc=286135 |bibcode=1969PNAS...64..121P |doi-access=free }}{{cite journal |last1=Phillips |first1=Herbert M. |last2=Steinberg |first2=Malcolm S. |date=1978 |title=Embryonic tissues as elasticoviscous liquids. I. Rapid and slow shape changes in centrifuged cell aggregates |url=https://pubmed.ncbi.nlm.nih.gov/649680/ |journal=J Cell Sci |volume=30 |pages=1–20 |doi=10.1242/jcs.30.1.1 |pmid=649680 |access-date=May 19, 2021}}

Later experiments led him to conclude that differential adhesion, and an adhesion gradient, guide the salamander pronephric duct to the cloaca during embryonic development.{{cite journal |last1=Steinberg |first1=Malcolm S. |last2=Poole |first2=Thomas J. |date=1981 |title=Strategies for specifying form and pattern: adhesion-guided multicellular assembly |url=https://pubmed.ncbi.nlm.nih.gov/6117905/ |journal=Philos Trans R Soc Lond B Biol Sci |volume= 295|issue=1078 |pages=451–60 |doi=10.1098/rstb.1981.0153 |pmid=6117905 |bibcode=1981RSPTB.295..451S |access-date=May 19, 2021}}

Steinberg completed his BS at Amherst College in 1952, his PhD in zoology at the University of Minnesota in 1956, was a professor of biology at Johns Hopkins University from 1958 to 1966, and transferred to Princeton University in 1966, becoming professor emeritus in 2005.