Spatial and temporal control of lipid-membrane morphology induced by sphingomyelinase

Sphingomyelinase (SMase) has been shown to be involved in a variety of cell regulation processes. It can convert sphingomyelin (SM) to ceramide (Cer) and has been suggested to influence the cellular processes by reorganizing the cell membrane morphology. This thesis aims at a more comprehensive understanding of how sphingomyelinase (SMase) can regulate lipid membrane heterogeneity. We develop corralled model raft membranes in a microfluidic device to study the complex phase phenomena induced by SMase. The mass balance of lipid molecules in each confined corral greatly helps us to interpret results. By using the corralled membrane arrays, we are able to obtain the overall statistical distribution of the induction time of a slow domain nucleation and therefore fairly compare the membrane responses caused by different factors. In addition, the flow control by a microfluidic device solves the difficulty of distributing SMase uniformly to membrane systems. Furthermore, the laminar flow in a microchannel allows us to create model membrane arrays with a variety of lipid membrane compositions or solution conditions, which can serve as a screening tool to study a broad range of parameters associated with the interactions between lipid membranes and SMase or other peripheral proteins. We report that SMase can induce both a reaction-induced and a solvent-mediated phase transformation, causing switches of three stationary membrane morphologies and multiple-time-domain ceramide generation in model raft membranes.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Chao, Ling, Ph. D. Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• Klavs F. Jensen, Alice P. Gast and T. Alan Hatton.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/51670

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/51670