FFFaaallllll 222000111000 SSSeeemmmiiinnnaaarrr SSSeeerrriiieeesss Department of Biomedical Engineering

Date Speaker Title

September 1 Introduction of CCNY BME Research Seminar Kickoff Day

September 8 Dr. Howard J. Hillstrom Director

Motion Analysis Laboratory Hospital for Special Surgery

Knee Osteoarthritis: the Role of Lower Extremity Structure and

Function

September 15 Dr. Ronald Koder Assistant Professor

Physics/CCNY

Protein design, synthetic biology and hybrid metamaterials

September 22 Dr. Stephen Cowin Professor

BME/CCNY

The specific growth rates of tissues; a review and a reevaluation

September 29

Danielle Wu BME/CCNY PhD Candidate

Stokesian Fluid Stimulus Probe for Delivery of Quantifiable Localized

picoNewton Level Forces for Cellular Excitation

October 6 BMES Annual Meeting No seminar

October 13 Dr. Chandra Kothapalli Postdoctoral Fellow

Department of Biological Engineering Massachusetts Institute of Technology

A high-throughput Microfluidic Device to Study Axonal Outgrowth

and Turning

October 20 Dr. Victor Rizzo Associate Professor

Cardiovascular Research Center Dept. of Anatomy and Cell Biology

Temple University School of Medicine

Plasma membrane microdomains integrate early

mechanotransduction events in endothelial cells exposed to shear

stress

October 27 Jerry Korten General Manager Strategic Markets

GE Healthcare

Epic Fail, Great Design versus the Clinical Value Proposition

November 10 Dr. Christopher J. Hernandez Assistant Professor

Mechanical and Aerospace Engineering Biomedical Engineering

Cornell University

Microstructural Flaws Associated with Bone Remodeling

November 17 Dr. Sang-woo Seo Assistant Professor

Electrical Engineering/CCNY

Integrated optical interfaces for multi-functional sensing systems

November 24 TBA

December 1 Dr. Jay Humphrey Professor

Department of Biomedical Engineering Texas A&M

Zweifach Lecture Fundamental Mechanical Roles of

Elastin in Arterial Homeostasis and Disease

December 8 Dr. Rao V.L.Papineni

Senior Principal Investigator, R&D

Carestream Health, Inc.

Howard J Hillstrom, Ph.D. Director, Leon Root, MD Motion Analysis Laboratory, Hospital for Special Surgery Knee Osteoarthritis: the Role of Lower Extremity Structure and Function Osteoarthritis (OA) is a disease that involves both biomechanical and biochemical factors that destabilize the cartilage matrix and cause pain, functional limitations, and disability. OA directly affects over 20 million people and is the leading cause of disability in the US. This talk will describe several studies that link lower extremity structure to biomechanical function. Foot and ankle, knee, and hip malalignment, increased BMI, and injury have all been associated with lower extremity OA onset and progression. Specific research examples will be described that examine the efficacy of conservative treatments, surgical treatments, and total joint replacement. The quest for biomarkers of the disease and the effect of treatment upon these biomarkers will be described --- is there a link between aberrant biomechanics and joint pathophysiology? One of the potential mechanisms for ACL injury, a known precursor to knee OA, will also be presented. An early view of a subject specific knee stress model will be shown towards the goal of predicting how malalignment and BMI may affect a specific patient and how treatment may alter that stress distribution. As the US populations ages the prevalence of OA is predicted to significantly rise including the demand for total joint replacements, joint sparing surgeries, and effective means of conservative care. OA may be one of the most challenging problems for which the biomechanics and bioengineering communities will be called upon for answers in the coming decade.

Dr. Ronald Koder, Assistant Professor, Physics/CCNY Protein design, synthetic biology and hybrid metamaterials The systemic analysis of photosynthesis led in the late 1980s to the bioinspired concept of ‘integrated modular assembly’ as a simple basis for constructing molecular devices, fashioned of any nanoscale material capable of holding the active elements at fixed distances, which can transform photonic energy into vectorial electron transfer. We describe our efforts in the de novo design of phthalocyanine-based charge separation protein domains which can be modularly attached via molecular Lego to other designed or natural protein domains and act as centers for light activated electron extraction and/or injection. We are coupling these materials to novel metamaterial electrodes which hold great promise as solid-state light harvesting and distribution materials in multi-junction biofuel-generating solar energy nanodevices.

The specific growth rates of tissues; a review and a reevaluation

Stephen C. Cowin, Professor The New York Center for Biomedical Engineering and

The Department of Mechanical Engineering The Department of Biomedical Engineering

Grove School of Engineering of The City College and The Graduate School of The City University of New York

New York, NY 10031, U. S. A.

Two distinct methods of modeling the growth of an organism were inspired by D’Arcy

Thompson’s method of coordinate transformations. One is based on the solid mechanics concept

of the deformation of an object and other based on the fluid mechanics concept of the velocity

field of a fluid. Although proposed more that 70 years ago, they were not given names until

recently. The solid mechanics model was called the distributed continuous growth (DCG) model

by Skalak et al. (1982) and the fluid mechanics model is called the graphical growth velocity

field representation (GVFR) by Cowin (2010). The GVFR is a minimum or simple model based

only on the assumption that a velocity fields may be used effectively to illustrate experimental

results that reveal the centers of growth and growth gradients first described by Julian Huxley in

1932. It is the method with a future that earlier writers considered, inappropriately, as an aspect

of the DCG model. The prospects for the DCG model itself are less attractive as it does not allow

mass change of the organism, does not recognized centers of growth and growth gradients and it

requires a closed system that permits no transport across it boundaries. These statements about

the literature are demonstrated with interesting and extensive graphic illustrations, mostly

historical.

References Cowin SC. 2010. Continuum kinematical modeling of mass increasing biological growth, Int. J.

Engr. Sci. in press, available online now. Huxley JS. 1932. Problems of Relative Growth, New York, Lincoln MacVeagh, 1st ed. (2nd ed.

1972 New York, Dover) Skalak R, DaGupta G, Moss M, Otten E, Dullemeijer P, Vilmann H. 1982. Analytical

description of growth, J. theor. Biol. 94:555-577

Stokesian fluid stimulus probe for delivery of quantifiable localized picoNewton level forces for cellular excitation Danielle Wu1, Peter Ganatos2, David C. Spray3, & Sheldon Weinbaum1

1Department of Biomedical Engineering, The City College of New York, 140th Street and Convent Avenue, New York, NY 10031, 2Department of Mechanical Engineering, The City College of New York,140th and Convent Avenue, New York, NY 10031, 3Dominick P. Purpura Department of Neuroscience and the Department of Medicine, Kennedy Center, Albert Einstein College of Medicne, Bronx, NY 10461 A new force probe capable of delivering quantifiable pN level hydrodynamic forces is developed to investigate cellular integrin attachments wherein it is no longer necessary to touch the cell or its substrate. This new technique called the Stokesian fluid stimulus probe (SFSP) differs from previous micropipette studies in that it functions in a flow regime where one can produce a nearly spherical highly repeatable fluid bolus. The hydrodynamic disturbance is a short lived (50-100 ms) weak pressure pulse that propagates nearly instantaneously through the medium. Although the bolus grows to several tens of microns, the pressure disturbance decays over a length scale of 2-5 microns producing pressure forces that vary from 1-30 pN/µm2 over this distance. Laboratory model experiments show that the growth of the bolus and the pressure field can be closely modeled by quasi-steady Stokes flow through a circular orifice provided the tip Reynolds number, Ret<0.03. The probe enables one to reproduce pN level forces similar to what a single cell experiences in its native environment. The new technique is ideal for exploring local mechanotransduction mechanisms on subcellular structures and is utilized herein to study electrophysiological responses of the osteocyte-like bone cells to localized pN level hydrodynamic forces in the physiological range. These results clearly show that cellular excitation occurs on the dendritic processes as opposed to the cell body and is likely due to an integrin-mediated stretch-activated ion channel.

A high-throughput Microfluidic Device to Study Axonal Outgrowth and Turning

Chandra Kothapalli, PhD Postdoctoral Fellow

Department of Biological Engineering Massachusetts Institute of Technology

Growth factor gradients have been implicated in many biological phenomena, including cell migration, axonal outgrowth and guidance in the nervous system. Current in vitro assays to study the effect of growth factors on axonal guidance are limited by their suitability for only substrate-bound gradients and 2D cultures. In this talk, I will discuss the design and implementation of a novel three-channel microfluidic device to study the role of chemogradients on axonal outgrowth and guidance in vitro. Within this device, neurons can be manipulated to extend their axons into the 3D gel, and the growing axons were exposed to a chemogradient orthogonal to the direction of their growth, to quantify their response and turning. Experimental and computational studies showed that a stable chemogradient could be established in these devices within 30 min and lasting for up to 48 h, after which gradient was reestablished. Cell culture studies revealed the dramatic effect of chemoattractive (netrin-1, brain pulp) and chemorepulsive (slit-2) gradients on the migration and axonal guidance of hippocampal and dorsal root ganglion neurons cultured in these devices. The stable chemogradients in these 3-channel devices could not only be used to screen potential drugs suitable for neuron pathway regeneration under disease/ injury conditions, but also to study cancer cell migration and cell-cell interactions.

Plasma Membrane Microdomains Integrate Early Mechanotransduction Events in

Endothelial Cells Exposed to Shear Stress Victor Rizzo, PhD, FAHA

Associate Professor Cardiovascular Research Group, Dept. of anatomy and Cell Biology

Temple University School of Medicine Distinct structures present on the surface of many cell types, especially the vascular endothelium, are the smooth, flask-shaped, invaginations called caveolae. Primarily described as transport vesicles involved in the processes of endocytosis and transcytosis, more recent studies have garnered great interest in caveolae because of their apparent role in signaling. Caveolin, which is a principle protein component of caveolar membranes, can directly interact with a variety of signaling molecules apparently leading to their inactivation. These signaling molecules become activated once receptor binding occurs in caveolae. The localization of receptors and signaling molecules within a small invaginated microdomain is likely to provide the proximity necessary for rapid, efficient and specific propagation of signals to downstream targets. Our previous work has identified caveolae as important mechanotransduction sites as increasing flow and pressure in situ stimulated protein-tyrosine phosphorylation within caveolae and stimulated NO production from caveolae associated endothelial nitric oxide synthase (eNOS). More recently, we reported that shear stress-induced activation of β1 integrin resulted in Src-family kinase (SFK) dependent phosphorylation of caveolin-1. This phosphorylation event served to recruite signaling molecules to integrin sites and propagate a mechano-signaling pathway which mediated endothelial cell adaptive responses to flow. These findings led us to formulate a central hypothesis that plasma membrane caveolae function as mechanotransduction centers. The long-range goal of our research in this area is to describe meaningful elements of the mechanotransduction process in endothelial cells to further understand the role of hemodynamics in the vascular homeostasis and disease. Our immediate focus is to determine whether caveolae served as initiation and integration sites to coordinate endothelial cell responses to hemodynamic shear stress. In order to achieve our goals, we use a variety of experimental approaches including subcellular fractionation, biochemical, molecular genetic and unique in vivo and in vitro techniques.

Epic Fail, Great Design versus the Clinical Value Proposition

Jerry Korten

General Manager Strategic Markets

GE Healthcare As Bioengineers and Scientists we strive to create products that

will become useful to the medical community and are a

commercial success. Yet we are trained to focus on the technical

details and the beauty of the design. Here is a cautionary story of

a product that was ahead of its time and missed the clinical value

proposition. How you should fail too, but early and often to help

your ideas and inventions become successful sooner.

Microstructural Flaws Associated with Bone Remodeling

Christopher J. Hernandez, Ph.D.

Assistant Professor Mechanical and Aerospace Engineering and Biomedical Engineering

Cornell University The amount of bone remodeling in the skeleton has been identified as a predictor of fracture risk independent of bone mineral density. While it is not known how increases in bone remodeling might influence bone strength, the most common explanation proposed is that cavities formed during the remodeling process (remodeling cavities) act as stress risers within bone, causing local tissue yielding and impairing mechanical performance at the whole bone level. To address this question we have advanced a sub-micron resolution three-dimensional fluorescence imaging approach known as serial milling. Serial milling imaging provides is first method to allow us to observe and measure the number and size of resorption cavities in cancellous bone structures (specimens ~ 3mm in size). Here I present the image analysis approach along recent findings regarding the changes in remodeling cavities associated with estrogen depletion. Additionally, high-resolution finite element models of individual resorption cavities are presented along with estimates of the elastic stress concentration factors associated with remodeling cavities. Future applications of this approach to the study of bone remodeling and failure processes in trabecular bone are discussed. Website: http://www.mae.cornell.edu/index.cfm/page/fac/hernandez.htm

Integrated Optical Interfaces for Multi-functional Sensing Systems

Sang-Woo Seo, PhD

Assistant Professor Department of Electrical Engineering

CCNY/CUNY There is a growing interest in developing lab-on-a chip systems performing

traditional bio/chemical laboratory measurements on samples with high

portability, high precision, and high throughput in an affordable cost.

Microfluidic technologies have allowed various fluidic functionalities.

However, they often require larger external interfaces for signal processing

and detection systems. This configuration becomes a serious limiting factor

posing all the issues related with reliability, sensitivity, complexity, and cost.

Intimate integration of different functional devices (such as optics, fluidics,

and electronics) on a system will greatly advance the field of lab-on-a chip.

In this talk, heterogeneous integration of thin film photonic devices will be

presented for multi-functional integrated systems. I will present our

approach to integrate different optical functions (source, detector, and

waveguides) with other functional devices for fully integrated lab-on-a

systems with optics, fluidics, and electronics.

Fundamental Mechanical Roles of Elastin in Arterial Homeostasis and Disease

J. D. Humphrey Department of Biomedical Engineering

Yale University, New Haven, CT The three primary structural constituents within the arterial wall are elastin, fibrillar collagens, and smooth muscle. It has long been thought that elastin plays a dominant mechanical role at low (non-physiologic) blood pressures whereas collagen plays a dominant role at higher (physiologic) blood pressures. In this talk, we will explore new data and computational models that reveal further the fundamental means by which elastin endows the arterial wall with unique characteristics as well as the consequences of its loss in hypertension, Marfan syndrome, and the formation of diverse aneurysms. Implications of these findings also relate to the origin of residual stress in arteries, their functional adaptations to altered hemodynamics, and tissue engineering.