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PNAS 104 (46): 18037-18042

Copyright © 2007 by the National Academy of Sciences.

From the Cover

BIOLOGICAL SCIENCES / BIOPHYSICS

Memory in receptor–ligand-mediated cell adhesion

Veronika I. Zarnitsyna*, Jun Huang*, Fang Zhang*, Yuan-Hung Chien{dagger}, Deborah Leckband{dagger}, and Cheng Zhu*,{ddagger},§

*Coulter Department of Biomedical Engineering and {ddagger}Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0363; and {dagger}Departments of Chemistry and Chemical and Biomolecular Engineering, University of Illinois at Urbana–Champaign, Urbana, IL 61801

Edited by Michael L. Dustin, Skirball Institute of Biomolecular Medicine, New York, NY, and accepted by the Editorial Board September 7, 2007

Received for publication May 22, 2007.

Abstract: Single-molecule biomechanical measurements, such as the force to unfold a protein domain or the lifetime of a receptor–ligand bond, are inherently stochastic, thereby requiring a large number of data for statistical analysis. Sequentially repeated tests are generally used to obtain a data ensemble, implicitly assuming that the test sequence consists of independent and identically distributed (i.i.d.) random variables, i.e., a Bernoulli sequence. We tested this assumption by using data from the micropipette adhesion frequency assay that generates sequences of two random outcomes: adhesion and no adhesion. Analysis of distributions of consecutive adhesion events revealed violation of the i.i.d. assumption, depending on the receptor–ligand systems studied. These include Markov sequences with positive (T cell receptor interacting with antigen peptide bound to a major histocompatibility complex) or negative (homotypic interaction between C-cadherins) feedbacks, where adhesion probability in the next test was increased or decreased, respectively, by adhesion in the immediate past test. These molecular interactions mediate cell adhesion and cell signaling. The ability to "remember" the previous adhesion event may represent a mechanism by which the cell regulates adhesion and signaling.

Key Words: adhesion frequency assay • Markov sequence • single-molecule mechanics • Bernoulli sequence

Author contributions: V.I.Z. and C.Z. designed research; J.H., F.Z., and Y.-H.C. performed research; D.L. contributed new reagents; V.I.Z. and C.Z. contributed new analytic tools; V.I.Z. and C.Z. analyzed data; and V.I.Z. and C.Z. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. M.L.D. is a guest editor invited by the Editorial Board.

This article contains supporting information online at www.pnas.org/cgi/content/full/0704811104/DC1.

§To whom correspondence should be addressed. E-mail: cheng.zhu{at}bme.gatech.edu

© 2007 by The National Academy of Sciences of the USA

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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