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Posted: Feb 24, 2006

NanoMedicine center strives to develop technologies for regenerative medicine

(Nanowerk News) Columbia University is a major contributor to the NanoMedicine Center for Mechanical Biology, a multi-disciplinary initiative aimed at developing new technologies for regenerative medicine and treating human diseases that involve mechanical malfunction, such as cancer.
The ultimate goal of the NanoMedicine Center for Mechanical Biology is to create an understanding of cellular mechanical biology which, once grasped, could lead to a pioneering operations manual for cell mechanical function. Since many diseases such as cancer, cardiovascular disease, osteoporosis, and immune disorders can originate from cell mechanical malfunction, this could provide important new technologies for treatments, i.e. a Cellular Repair Manual.
Funding for the center stems from a National Institute of Health (NIH) Roadmap Initiative grant, consisting of $1.4 million a year for five years. The goal of the grant is to encourage bio-medical researchers and engineers to build upon existing nanotechnologies (in this instance, at the Columbia Nanotechnology Center) and design a second generation of technologies to understand the interaction of complex biological systems in health and disease.
This is an international group that brings technologies from Switzerland, Israel and Germany to six labs at Columbia and to labs at Mt. Sinai Hospital and NYU Medical Center. At Columbia, the NanoMedicine Center for Mechanical Biology consists of six working groups (see below) and will avail itself of extant multi-disciplinary expertise and groundbreaking advances in many areas of science. The center will tap into the university's expertise in varied science realms, especially nanomedicine.*
Columbia Professor of Cell Biology, Michael Sheetz, a formative member of the center, says its creation places the university in a unique category of advanced nanotechnology based research. " The new NanoMedicine Center for Mechanical Biology is a significant achievement for the university, and is one of only four in the entire country."
The other NIH funded centers are: the University of California at San Francisco's Engineering Cellular Control: Synthetic Signaling and Motility Systems Center; The University of Illinois Urbana-Champaign's National Center for Design of Biomimetic Nanoconductors, and Baylor College of Medicine's Center for Protein Folding Machinery.
The rationale for the Columbia center is based in part on the idea that while science today understands many of the inner workings of cell biochemistry, far less is known about the crucial intricacies of the mechanical aspects of cells (a process that, for example, allows 40 micron cells to determine the shape of an organism many meters its size), or how tissue become malformed when attacked by cancers and other diseases. Understanding and deciphering the underlying mechanisms of cellular mechanics could produce profound and fundamental new insights into how the processes of cell migration, metastasis, immune function and other areas which are regulated by mechanical forces. The technologies developed in the center will enable new treatments of those disorders.
Sheetz says, "Understanding the processes whereby cells sense and shape their mechanical environment is critical."
This is because cells respond to primary mechanical cues (of 'force' and 'geometry') through a complex procedure that begins at the molecular level. When intracellular systems sense these factors (i.e. 'force') they transduce (convert) cues into biochemical signals which are then processed to give mechanoresponses, which are then fed back to change the mechanical cues. The cumulative effect of these cycles determines whether a cell grows or dies, the shape of the organism, and the eventual effectiveness of many tissue functions.
Defects in areas such as mechanosensing and transduction underlie diseases including many cancers, immune disorders, genetic malformations and neuropathies. In other words, says Sheetz, "Appropriate cell behavior involves a test of the environment and knowing that the environment has the proper physical characteristics."
For insight into these mechanisms and processes the NanoMedicine Center for Mechanical Biology is adopting a three-pronged study approach: developing detailed quantitative pictures of the cellular machinery at the single-molecule level, (how single molecules respond to force); on the nanoscale level, describing how supramolecular complexes regulate each other, and understanding how forces regulate signaling pathways and gene expression.
Chris Wiggins, professor of applied physics and applied mathematics at Columbia and a center member, says, "In addition to pioneering experimental approaches using nanotechnology, we hope to learn how physical information, in the form of forces and constraints, transforms into chemical information, and finally genetic information."
To bring these goals to fruition, and to create a fuller understanding of cellular processes especially on a systems bioengineering level, the center is tapping into a diverse array of expertise including scientists, engineers and applied mathematicians who will focus on mechano-transduction (the process by which cells convert mechanical stimuli into biochemical signals) at the cell and molecular level. On the nanoscale level the center is assembling expertise and will utilize cutting-edge technologies from biologists, chemists, engineers and computational scientists in novel and unique ways. Researchers from Mt. Sinai School of Medicine, the Weizmann Institute, the NYU Skirball Institute and ETH Polyteknium Zurich, are also involved.
A preliminary list of NanoMedicine Center for Mechanical Biology investigators ( Columbia and non-Columbia):

Team Member

Area of Research & Tools

Martin Chalfie
(Biological Sciences, Columbia University)

Force sensing in vivo, genetic modulation neural function, development of optical probes

Michael Dustin
(Immunology, NYU Medical Center)

Role of motility and spacing in immune synapse function

Benjamin Geiger
(Dept of Molecualr Cell Biology, Weizmann Institute)

Cancer cell motility and function, Bone formation and resorption

James Hone
(Mechanical Eng. Columbia University)

Development of micro and nanodevices for biological applications

Ravi Iyengar
(Pharmacology Department, Mt. Sinai Medical Center)

Application of signal pathway modeling to understand cellular functions

Lance Kam
(Bio-Med Engineering) Columbia University)

Membrane protein dynamics in cell-cell contact formation and immune synapse function

Michael Sheetz*
(Biological Sciences, Columbia University)

Force effects on cell function in wound healing and metastasis

Viola Vogel
(Department of Materials, ETH Polyteknium, Zurich)

Force effects on matrix formation and function, engineering of matrices to regulate specific cell functions

Chris Wiggins
(Applied Mathematics and Physics, Columbia University)

Functional pattern recognition in biological systems and systems analysis of biological functions

Shalom Wind
(Applied Physics, Columbia University)

Development of nanometer level devices for probing or manipulating biological function

Nanomedicine is the study of the medically relevant processes both physical and biochemical at the subcellular (nanometer) level and unquestionably holds the greatest potential for revealing insights into bio-mechanical cellular activity. Technologies can then be developed into treatments and therapies. To learn more about this developing field visit the NIH Web site.

Source: Columbia University
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