2014 — 2015 |
Schneider, Ian Christopher |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Probing Contact Guidance On Exquisitely Tunable Ecm Surfaces
DESCRIPTION (provided by applicant): It has been long appreciated that changes in the extracellular matrix (ECM) in the tumor microenvironment can drive tumor progression. With the recent advance in imaging techniques changes in the organization of ECM components like collagen have been described. Circumferentially organized collagen fibers are reorganized into radially aligned fibers, leading to directed migration or contact guidance away from the tumor. This collagen organizational signature has been proposed as a diagnostic indicator of potential invasion, linking contact guidance to invasion. Unfortunately, while there is an abundance of information on contact guidance in 2D environments, much less is known about contact guidance in 3D environments. In addition, collagen fiber networks can exhibit a large variation in properties separate from alignment that regulate the ability of cells to sense and respond to contact guidance cues, effectively altering the relationship between collagen organization and invasion. My long-term goal is to understand how tumor, stromal and immune cells integrate multiple cues for directional migration in the tumor microenvironment by using various engineering approaches. The objective of this research is to understand the role of the organization and composition of collagen I matrix in directing contact guidance. The specific aims of this proposal include: (1) Assess the relative contributions of topology and confinement in explaining the differences between contact guidance in 2D and 3D environments, (2) Test the hypothesis that changes in fiber structure such as fiber and crosslinking density as well as degree of alignment regulate the contact guidance of cancer cells and (3) Test the hypothesis that collagen I binding proteins that promote adhesion or de-adhesion regulate the contact guidance of cancer cells. Epitaxial growth of collagen fibers on mica as well as magnetic alignment of collagen fibers in gels will be used to engineer environments with specify contact guidance characteristics. Cell migration will be assessed using live cell microscopy in 2D, 3D and hybrid environments. Understanding how different properties of collagen fiber networks regulate contact guidance will further refine the prognostic ability of diagnostic biopsy images. Quantification of collagen fiber density, measurement of mechanical properties of the biopsy, a proxy for crosslinking density, and staining of additional collagen binding partners will give insight into the efficiency of contact guidance away from an individual tumor. Future work will be geared towards making these measurements in vivo and in biopsies from mouse tumor models and correlating these biophysical and compositional properties to tumor progression or prognosis.
|
1 |
2016 — 2019 |
Jiles, David (co-PI) [⬀] Que, Long [⬀] Schneider, Ian Hadimani, M |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
On-Chip Studies of Neuron Cells Under Magnetic Field Stimulation
Proposal Title: On-chip studies of neuron cells under magnetic field stimulation Brief description of project Goals:
This project is to develop a microchip for studying the single neuron cells and their interaction under magnetic field stimulation.
Nontechnical Abstract: One in five Americans above the age of 18 suffer from diagnosable neurological disorders and there are 50,000 new cases of Parkinson's disease diagnosed every year in the United States. 10 to 20% of apparently healthy service members returning from conflicts in Iraq and Afghanistan suffer from post-traumatic stress disorder (PTSD). Therefore there is a critical need to develop new, safe, non-invasive methods for the treatment of deep brain disorders. Non-invasive techniques including repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have had some success, but progress has been limited because of poor understanding of interaction of magnetic fields with neurons. Basically the molecular/cellular mechanisms of neurons under TMS are still lacking. To address these issues, the scientific and technical component of this project focuses on the investigation of the effect of transient magnetic fields on the neuronal growth rate and synaptic activity, which is essential in developing new treatment procedures for debilitating neurological disorders such as Parkinson's disease, PTSD and traumatic brain injury. The education, dissemination and outreach component of this project includes mentoring graduate, undergraduate and underrepresented/minority students, dissemination and outreach to the local community. The overall educational goal is to help next-generation workforce development by training students to carry out research with sound technical background and allowing them to gain hands-on laboratory skills for their advanced careers.
Technical Abstract: The proposed project seeks to develop an integrated microchip that allows, for the first time, studying the growth, synaptic activity and regeneration of single neuron cells and interaction among the separated neuron cells under both AC/transcranial magnetic and DC magnetic field stimulation. Specifically, this project focuses on: (i) the development of a new microchip, which consists of microholder arrays with integrated patch-clamp probes to store single neuron cells; (ii) the study of the growth behavior and monitoring of the action potential of single neuron cells (N27 cells and PC12 cells as the models) under AC/transcranial magnetic field stimulation; (iii) the study of the growth behavior of the neuron cells inside a 3D extracellular matrix, mimicking the in vivo environment, under AC/transcranial magnetic field stimulation; and (iv) the study of the guided neuron growth by functionalizing the neuron cells with magnetic nanoparticles (mNPs) under DC and AC/transcranial magnetic field stimulation. This proposed research may help advance fundamental knowledge of growth and regeneration of single neuron cells under the magnetic field stimulation, which might have significant impact on the field of regenerative medicine from both scientific and engineering points of view. This proposed integrated technical platform offers some unique features otherwise unavailable by any other existing platforms, providing the capability for monitoring the behaviors of single neuron cells and the interactions among them. These functions in this platform might help trigger some basic discoveries, some important ideas and innovations for biomedical applications.
|
0.915 |
2021 |
Schneider, Ian Christopher |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cell Migration Control Through Modulation of Multiple Directional Cues
ABSTRACT The goal of this project is to use engineered extracellular matrix environments leveraging structural and me- chanical control over the extracellular matrix to examine the mechanisms by which cells respond to multiple directional migration cues. Cell migration plays an important role in many physiological and pathological pro- cesses such as wound healing, development and cancer invasion. Frequently migration is not simply random, but directed towards targets through recognition of aligned extracellular matrix fibers or gradients in stiffness, generating contact guidance and durotaxis, respectively. In many biological contexts these cues are presented simultaneously, forcing cells to integrate this information. For instance, gradients of stiffness and aligned colla- gen are generated within the wound bed to direct dermal fibroblast migration. Similar fiber structures and gra- dients stimulate cancer cell migration out of the tumor microenvironment and normal cells including stromal and immune cells towards the tumor microenvironment. While there is a firm understanding of how cells re- spond to individual directional cues, virtually nothing is known about how cells integrate multiple cues and make migrational decisions based on that integration. Furthermore, there is a hypothesis that contact guidance and durotaxis are overlapping directional cell migration mechanisms, but this has not been rigorously tested. Mechanistic understanding of multi-cue directional migration will require a refined understanding of how the F- actin and microtubule networks operates. Indeed, some evidence suggests that contact guidance and durotax- is may use slightly different F-actin network structures, since contact guidance is thought to be governed by F- actin fiber structures, but durotaxis is not. Engineering approaches will be taken to design in vitro environments that allow for independent tuning of contact guidance and durotaxis in both 2D and 3D environments. Further- more, the effect of F-actin branching, bundling and contraction in allowing cells to prefer aligned fibers of colla- gen or gradients of stiffness will be tested. This will uncover shared or competing molecular pathways involved when these two directional migration cues are present in isolation and together. Understanding how cells mi- grate in response to multiple cues has broad impact on several biomedical fields including tissue engineering and disease therapeutics. Determining how cells respond to multiple cues in vitro will allow us to predict cell responses in wound healing, development, cancer invasion and immune response leading to drug candidates as in cancer or strategies to enhance wound healing and immune response.
|
1 |