Engineering Commons^™

Mechanical Properties And Morphological Alterations In Fiber-Based Scaffolds Affecting Tissue Engineering Outcomes, James Dolgin, Samerender Nagam Hanumantharao, Stephen Farias, Carl G. Simon, Smitha Rao

Michigan Tech Publications

Electrospinning is a versatile tool used to produce highly customizable nonwoven nanofiber mats of various fiber diameters, pore sizes, and alignment. It is possible to create electrospun mats from synthetic polymers, biobased polymers, and combinations thereof. The post-processing of the end products can occur in many ways, such as cross-linking, enzyme linking, and thermal curing, to achieve enhanced chemical and physical properties. Such multi-factor tunability is very promising in applications such as tissue engineering, 3D organs/organoids, and cell differentiation. While the established methods involve the use of soluble small molecules, growth factors, stereolithography, and micro-patterning, electrospinning involves an inexpensive, labor …

Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn

Publications and Research

Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme …

A Single Cell Pair Mechanical Interrogation Platform To Study Cell-Cell Adhesion Mechanics, Amir Monemianesfahani

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

The Role Of Microenvironmental Cues And Mechanical Loading Milieus In Breast Cancer Cell Progression And Metastasis, Brandon D. Riehl, Eunju Kim, Tasneem Bouzid, Jung Yul Lim

Department of Mechanical and Materials Engineering: Faculty Publications

Cancer can disrupt the microenvironments and mechanical homeostatic actions in multiple scales from large tissue modification to altered cellular signaling pathway in mechanotransduction. In this review, we highlight recent progresses in breast cancer cell mechanobiology focusing on cell-microenvironment interaction and mechanical loading regulation of cells. First, the effects of microenvironmental cues on breast cancer cell progression and metastasis will be reviewed with respect to substrate stiffness, chemical/topographic substrate patterning, and 2D vs. 3D cultures. Then, the role of mechanical loading situations such as tensile stretch, compression, and flow-induced shear will be discussed in relation to breast cancer cell mechanobiology and …

The Role Of Microenvironmental Cues And Mechanical Loading Milieus In Breast Cancer Cell Progression And Metastasis, Brandon D. Riehl, Eunju Kim, Tasneem Bouzid, Jung Yul Lim

Department of Mechanical and Materials Engineering: Faculty Publications

Cancer can disrupt the microenvironments and mechanical homeostatic actions in multiple scales from large tissue modification to altered cellular signaling pathway in mechanotransduction. In this review, we highlight recent progresses in breast cancer cell mechanobiology focusing on cell-microenvironment interaction and mechanical loading regulation of cells. First, the effects of microenvironmental cues on breast cancer cell progression and metastasis will be reviewed with respect to substrate stiffness, chemical/topographic substrate patterning, and 2D vs. 3D cultures. Then, the role of mechanical loading situations such as tensile stretch, compression, and flow-induced shear will be discussed in relation to breast cancer cell mechanobiology and …

The Glycocalyx And Its Role In Vascular Physiology And Vascular Related Diseases, Sheldon Weinbaum, Limary M. Cancel, Bingmei M. Fu, John M. Tarbell

Publications and Research

Purpose—In 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121–167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.

Methods—A literature search mainly focusing on the role of the glycocalyx in the two major areas described above …

The Linc Complex, Mechanotransduction, And Mesenchymal Stem Cell Function And Fate, Tasneem Bouzid, Eunju Kim, Brandon D. Riehl, Amir Monemian Esfahani, Jordan Rosebohm, Ruiguo Yang, Bin Duan, Jung Yul Lim

Department of Mechanical and Materials Engineering: Faculty Publications

Mesenchymal stem cells (MSCs) show tremendous promise as a cell source for tissue engineering and regenerative medicine, and are understood to be mechanosensitive to external mechanical environments. In recent years, increasing evidence points to nuclear envelope proteins as a key player in sensing and relaying mechanical signals in MSCs to modulate cellular form, function, and differentiation. Of particular interest is the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that includes nesprin and SUN. In this review, the way in which cells can sense external mechanical environments through an intact nuclear envelope and LINC complex proteins will be briefly described. Then, …

Stretch Control Of Adipocyte Insulin Signaling, Tasneem Bouzid

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Obesity and related metabolic disorders have reached global epidemic proportions in recent decades. Excess and hypertrophic adipose tissue has been implicated in the development of various pathological diseases and disorders including Type-2 diabetes mellitus (Type-2 DM). In addition to serving as energy storage for the body, evidence also suggests that adipose tissue behaves as an endocrine organ capable of secreting bioactive cytokines known as adipokines, which mediate insulin signaling pathways in various tissues. Physical exercise has been demonstrated to positively affect insulin signaling activities potentially through increasing the secretion of insulin sensitizing adipokines and/or decreasing the secretion of pro-inflammatory insulin …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …

Tumor Vessel Normalization After Aerobic Exercise Enhances Chemotherapeutic Efficacy., Keri L Schadler, Nicholas J Thomas, Peter Galie, Dong Ha Bhang, Kerry C Roby, Prince Addai, Jacob E Till, Kathleen Sturgeon, Alexander Zaslavsky, Christopher S Chen, Sandra Ryeom

Henry M. Rowan College of Engineering Faculty Scholarship

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical …

Biomimetic Substrate Control Of Cellular Mechanotransduction, Mohammad Nahid Andalib, Yuris A. Dzenis, Henry J. Donahue, Jung Yul Lim

Department of Mechanical and Materials Engineering: Faculty Publications

Extracellular mechanophysical signals from both static substrate cue and dynamic mechanical loading have strong potential to regulate cell functions. Most of the studies have adopted either static or dynamic cue and shown that each cue can regulate cell adhesion, spreading, migration, proliferation, lineage commitment, and differentiation. However, there is limited information on the integrative control of cell functions by the static and dynamic mechanophysical signals. For example, a majority of dynamic loading studies have tested mechanical stimulation of cells utilizing cultures on flat surfaces without any surface modification. While these approaches have provided significant information on cell mechanotransduction, obtained outcomes …

Fluid Flow-Induced Mesenchymal Stem Cell Migration: Role Of Fak And Rock Mechanosensors, Brandon D. Riehl

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

The study of mesenchymal stem cell (MSC) migration under mechanical stimulation conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcomes in stem cell-based regenerative medicine. MSCs having multipotent regenerative capability exist in niches in the bone marrow, muscle, vasculature, and in other tissues throughout the body, and their migration through tissues and vasculature for the repair of damaged tissue is a key process of cell and tissue homeostasis, remodeling, and regeneration. While cell migration in response to cytokines and other chemo-attractants is relatively well understood, little is revealed in regard to the effect …

The Role Of Mechanically Induced Erk Phosphorylation In Stem Cell Adipogenesis, Daniel E. Menter

Department of Engineering Mechanics: Dissertations, Theses, and Student Research

Mechanical cell stimulation has only recently been highlighted for its ability to direct cell function and fate. The development of techniques to apply controlled mechanical stimulation to cells has allowed researchers to examine the effects of forces on cell behavior. These studies have shown that cells, and in particular, stem cells are very sensitive to mechanical stimuli. While the potential impact of mechanical forces has been demonstrated by these studies, there have not been many studies that compare the differing effects of stimulation profiles and methods. Further, molecular mechanosensing mechanisms have not been identified. In this work, we compared the …

Macro And Microfluidic Flows For Skeletal Regenerative Medicine, Brandon D. Riehl, Jung Yul Lim

Department of Mechanical and Materials Engineering: Faculty Publications

Fluid flow has a great potential as a cell stimulatory tool for skeletal regenerative medicine, because fluid flow-induced bone cell mechanotransduction in vivo plays a critical role in maintaining healthy bone homeostasis. Applications of fluid flow for skeletal regenerative medicine are reviewed at macro and microscale. Macroflow in two dimensions (2D), in which flow velocity varies along the normal direction to the flow, has explored molecular mechanisms of bone forming cell mechanotransduction responsible for flow-regulated differentiation, mineralized matrix deposition, and stem cell osteogenesis. Though 2D flow set-ups are useful for mechanistic studies due to easiness in in situ and post-flow …

Systems And Synthetic Biology Of The Vessel Wall, Jennifer Frueh, Nataly Maimari, Ying Lui, Zoltan Kis, Vikram Mehta, Negin Pormehr, Calum Grant, Emmanuel Chalkias, Mika Falck-Hansen, Sandra Bovens, Ryan M. Pedrigi, Taka Homma, Gianfillippo Coppola, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

Atherosclerosis is intimately coupled to blood flow by the presence of predilection sites. The coupling is through mechanotransduction of endothelial cells and approximately 2000 gene are associated with this process. This paper describes a new platform to study and identify new signalling pathways in endothelial cells covering an atherosclerotic plaque. The identified networks are synthesized in primary cells to study their reaction to flow. This synthetic approach might lead to new insights and drug targets.

The Effect Of Physiological Cyclic Stretch On The Cell Morphology, Cell Orientation And Protein Expression Of Endothelial Cells, V. Barron, Claire Brougham, K. Coghlan, C. Stenson-Cox, D. O'Mahoney, P.E. Mchugh

Articles

In vivo, endothelial cells are constantly exposed to pulsatile shear and tensile stresses. The main aim of this study was to design and build a physiological simulator, which reproduced homogenous strain profiles of the tensile strain experienced in vivo, and to investigate the effect of this cyclic tensile strain on the cell morphology, cell orientation and protein expression of endothelial cells. The biological response of human umbilical vein endothelial cells to a uniaxial cyclic stretch, in this newly developed simulator, was examined experimentally using immunohistostaining and confocal imaging and it was

found that the cells elongated and oriented at 58.9± …

Mechano-Biological Interactions Of Endothelial Cells, Claire Brougham, Karen Coughlan, Valerie Barron, Peter Mchugh

Conference Papers

Atherosclerosis is an ever-increasing cause of morbidity in the western world. Current surgical treatments include bypass grafts and coronary artery stents. However, there is still a need for alternative approaches especially for those who cannot receive conventional therapy. Tissue engineering is one such approach that may hold the key to the repair and regeneration. Tissue engineering is one such approach that may hold the key to the repair and regeneration of coronary arteries. Nevertheless, many questions need to be answered before a vialbe vascular tissie with the inherent properties of native tissue becomes a real contender with the surgical therapies …