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Manoj Gopalakrishnan

Bio: Manoj Gopalakrishnan is an academic researcher from Indian Institute of Technology Madras. The author has contributed to research in topics: Ligand (biochemistry) & Microtubule. The author has an hindex of 10, co-authored 43 publications receiving 431 citations. Previous affiliations of Manoj Gopalakrishnan include Max Planck Society & Virginia Tech.

Papers
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Journal ArticleDOI
TL;DR: A novel mechanism whereby heparin catalyzes the conversion of fibronectin to an open conformation by transiently interacting with fibronECTin and progressively hopping from molecule to molecule is indicated.

77 citations

Journal ArticleDOI
TL;DR: A continuum stochastic formalism is developed to address how receptor clustering might influence ligand rebinding and finds that clusters reduce the effective dissociation rate dramatically when the clusters are dense and the overall surface density of receptors is low.

70 citations

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TL;DR: The analysis of the IGF-I–IGFBP-3 data indicates that rebinding is prominent for this system and that the theoretical predictions fit the experimental data well, and it is shown that this function is nonexponential at all times, indicating that multiple rebinding events strongly influence dissociation even at early times.
Abstract: Rebinding of dissociated ligands from cell surface proteins can confound quantitative measurements of dissociation rates important for characterizing the affinity of binding interactions. This can be true also for in vitro techniques such as surface plasmon resonance (SPR). We present experimental results using SPR for the interaction of insulin-like growth factor-I (IGF-I) with one of its binding proteins, IGF binding protein-3 (IGFBP-3), and show that the dissociation, even with the addition of soluble heparin in the dissociation phase, does not exhibit the expected exponential decay characteristic of a 1:1 binding reaction. We thus consider the effect of (multiple) rebinding events and, within a self-consistent mean-field approximation, we derive the complete mathematical form for the fraction of bound ligands as a function of time. We show that, except for very low association rate and surface coverage, this function is nonexponential at all times, indicating that multiple rebinding events strongly influence dissociation even at early times. We compare the mean-field results with numerical simulations and find good agreement, although deviations are measurable in certain cases. Our analysis of the IGF-I-IGFBP-3 data indicates that rebinding is prominent for this system and that the theoretical predictions fit the experimental data well. Our results provide a means for analyzing SPR biosensor data where rebinding is problematic and a methodology to do so is presented.

34 citations

Journal ArticleDOI
TL;DR: The mean search time for a single target by microtubules from a single nucleating site is computed using a systematic and rigorous theoretical approach, for arbitrary kinetic parameters, and is extended to multiple targets and nucleating sites by physical arguments.

31 citations

Journal ArticleDOI
01 Aug 2008-EPL
TL;DR: In this article, the authors developed a quantitative model to study the depolymerizing action of a generic motor protein, and its possible effects on the length distribution of microtubules.
Abstract: In many intracellular processes, the length distribution of microtubules is controlled by depolymerizing motor proteins. Experiments have shown that, following non-specific binding to the surface of a microtubule, depolymerizers are transported to the microtubule tip(s) by diffusion or directed walk and, then, depolymerize the microtubule from the tip(s) after accumulating there. We develop a quantitative model to study the depolymerizing action of such a generic motor protein, and its possible effects on the length distribution of microtubules. We show that, when the motor protein concentration in solution exceeds a critical value, a steady state is reached where the length distribution is, in general, non-monotonic with a single peak. However, for highly processive motors and large motor densities, this distribution effectively becomes an exponential decay. Our findings suggest that such motor proteins may be selectively used by the cell to ensure precise control of MT lengths. The model is also used to analyze experimental observations of motor-induced depolymerization.

24 citations


Cited by
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Journal ArticleDOI
TL;DR: Van Kampen as mentioned in this paper provides an extensive graduate-level introduction which is clear, cautious, interesting and readable, and could be expected to become an essential part of the library of every physical scientist concerned with problems involving fluctuations and stochastic processes.
Abstract: N G van Kampen 1981 Amsterdam: North-Holland xiv + 419 pp price Dfl 180 This is a book which, at a lower price, could be expected to become an essential part of the library of every physical scientist concerned with problems involving fluctuations and stochastic processes, as well as those who just enjoy a beautifully written book. It provides an extensive graduate-level introduction which is clear, cautious, interesting and readable.

3,647 citations

Journal ArticleDOI
TL;DR: Changing views on the specificity of protein-heparan sulfate binding and the activity of HSPGs as receptors and coreceptors are discussed.
Abstract: Heparan sulfate proteoglycans are found at the cell surface and in the extracellular matrix, where they interact with a plethora of ligands. Over the last decade, new insights have emerged regarding the mechanism and biological significance of these interactions. Here, we discuss changing views on the specificity of protein-heparan sulfate binding and the activity of HSPGs as receptors and coreceptors. Although few in number, heparan sulfate proteoglycans have profound effects at the cellular, tissue, and organismal level.

1,251 citations

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TL;DR: In this overview, 13 papers that should be on everyone's ‘must read’ list for 2003 are spotlighted and examples of how to identify and interpret high‐quality biosensor data are provided.
Abstract: In the year 2003 there was a 17% increase in the number of publications citing work performed using optical biosensor technology compared with the previous year. We collated the 962 total papers for 2003, identified the geographical regions where the work was performed, highlighted the instrument types on which it was carried out, and segregated the papers by biological system. In this overview, we spotlight 13 papers that should be on everyone's 'must read' list for 2003 and provide examples of how to identify and interpret high-quality biosensor data. Although we still find that the literature is replete with poorly performed experiments, over-interpreted results and a general lack of understanding of data analysis, we are optimistic that these shortcomings will be addressed as biosensor technology continues to mature.

518 citations

Journal Article
TL;DR: The authors do a superb job of selecting the material for each chapter and explaining the material with equations and narrative in an easily digestible manner, and this textbook is an excellent resource for a research scientist and for a teacher.
Abstract: Physical Biology of the Cell, 2nd Edition, is a textbook that focuses on the application of physical principles to understanding biological systems. The subject matter of the text is organized according to common physical principles that govern biological processes rather than in relation to the biological processes themselves, as is common for most biology and cell biology textbooks. Topics covered in the book span a broad range of interests, including electrostatics, molecular interactions, molecular motors and the cytoskeleton, and membranes. Each chapter features color figures, derived equations with relevant examples, and problem sets at the chapter’s conclusion. The problem sets at the end of the chapters are expanded from the first edition. Further, the second edition includes two new chapters, one on light and pattern formation, and another on the use of computation in exploring biological problems. Additional student and instructor resources are also available online. The primary audience for the textbook could include advanced undergraduate students or first-year graduate students. While the textbook may be best suited for a biophysics course, it could also be used as a primary or supplementary text for teaching cellular and molecular biology. As a teaching tool for cellular and molecular biology, the many examples featured throughout the text could easily be employed to assist students in learning the principles of how a cellular or molecular system functions. A basic level of mathematical proficiency would be required of the student. While this textbook could be an excellent resource for many courses, there are several topics commonly covered in biochemistry classes, such the glycolytic pathway, that are featured in the book but in different contexts than many widely used biochemistry texts. For a biophysics course that is heavily focused on techniques, individual references that discuss the specific techniques in detail would be more suitable than this book. Of course, any instructor seeking to use this textbook should be aware of its content before making a selection. This textbook is an excellent resource, both for a research scientist and for a teacher. The authors do a superb job of selecting the material for each chapter and explaining the material with equations and narrative in an easily digestible manner. Readers who enjoy this book may also enjoy Molecular Driving Forces by Dill and Bromberg, which gives excellent treatment of similar concepts.

491 citations

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TL;DR: Fibrin and its heparin-binding domain is incorporated into a synthetic fibrin-mimetic matrix to prove this role in a gain-of-function model and demonstrate the benefits of generating a hybrid biomaterial consisting of a synthetic polymeric scaffold and recombinant bioactive ECM domains.
Abstract: By binding growth factors (GFs), the ECM tightly regulates their activity. We recently reported that the heparin-binding domain II of fibronectin acts as a promiscuous high-affinity GF-binding domain. Here we hypothesized that fibrin, the provisional ECM during tissue repair, also could be highly promiscuous in its GF-binding capacity. Using multiple affinity-based assays, we found that fibrin(ogen) and its heparin-binding domain bind several GFs from the PDGF/VEGF and FGF families and some GFs from the TGF-β and neurotrophin families. Overall, we identified 15 unique binding interactions. The GF binding ability of fibrinogen caused prolonged retention of many of the identified GFs within fibrin. Thus, based on the promiscuous and high-affinity interactions in fibrin, GF binding may be one of fibrin’s main physiological functions, and these interactions may potentially play an important and ubiquitous role during tissue repair. To prove this role in a gain-of-function model, we incorporated the heparin-binding domain of fibrin into a synthetic fibrin-mimetic matrix. In vivo, the multifunctional synthetic matrix could fully mimic the effect of fibrin in a diabetic mouse model of impaired wound healing, demonstrating the benefits of generating a hybrid biomaterial consisting of a synthetic polymeric scaffold and recombinant bioactive ECM domains. The reproduction of GF–ECM interactions with a fibrin-mimetic matrix could be clinically useful, and has the significant benefit of a more straightforward regulatory path associated with chemical synthesis rather than human sourcing.

407 citations