Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Investigation into changes of the biophysical properties of basement membranes by atomic force microscopy

Candiello, Joseph Eugene (2010) Investigation into changes of the biophysical properties of basement membranes by atomic force microscopy. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (5MB) | Preview


Basement membranes (BMs) are sheets of extracellular matrix that separate epithelia from connective tissues and outline muscle fibers and the endothelial lining of blood vessels. A major function of basement membranes is to establish and maintain stable tissue borders. We introduce the inner limiting membrane (ILM), located at the retinal-vitreal junction, as a model system for studying the biophysical properties of BM. We also introduced atomic force microscopy techniques as important tools to investigate the ILM under physiologically relevant conditions. We were able to determine changes in both the thickness and elasticity of chick ILM during embryonic development. We also determined that BMs are much thicker in their native state than previously thought. Proteoglycans, specifically their heparan sulfate side-chains, were found to significantly contribute to ILM biophysical properties. The effects of aging on the composition, structure, and biophysical properties of the adult human ILM were investigated. A compositional shift in the ILM was associated with an increase in both the ILM thickness and elastic modulus during aging. The role of heparan sulfate molecules in the human ILM was determined to be similar to that of the chick ILM. The biophysical changes in mouse knockout models for congenital muscular dystrophy were also investigated. These models had protein knockouts that inhibit the proper formation of basement membranes. There were differences in the biophysical properties along with visually noted disruptions in the mouse inner limiting membranes due to improper formation of the BM. This study provided novel insight into the biophysical importance of BMs and the ability to study changes associated with a variety of biological conditions that are relevant to proper biological function, in addition to setting a baseline for the biophysical properties of BMs.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Candiello, Joseph Eugenejec40@pitt.eduJEC40
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairShroff, Sanjeevsshroff@pitt.eduSSHROFF
Committee CoChairHalfter, Williwhalfter@pitt.eduWHALFTER
Committee MemberSacks, Michael Smsacks@pitt.eduMSACKS
Committee MemberAbramowitch, Steven Dsdast@pitt.eduSDAST
Date: 26 January 2010
Date Type: Completion
Defense Date: 27 October 2009
Approval Date: 26 January 2010
Submission Date: 19 November 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: extra cellular matrix; inner limiting membrane; mechanical stiffness
Other ID:, etd-11192009-203915
Date Deposited: 10 Nov 2011 20:05
Last Modified: 15 Nov 2016 13:51


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item