The Singer-Nicholson fluid mosaic model characterized the plasma membrane as a """"""""two-dimensional oriented solution of integral proteins .....in the viscous phospholipid bilayer"""""""". Now, new information is forcing revision of some aspects of the model and has the potential to greatly enhance our understanding of membrane microstructure and its relation to cell function in normal and pathological situations. This information comes from attaching small particles to single or small groups of membrane components and following the motion of the particle with video microscopy or dragging the particle with the so called laser tweezers. Most proteins and even some lipids do not exhibit continuous, unrestricted lateral diffusion expected in a two-dimensional fluid. For example, many membrane components are transiently confined to small, submicron zones in seemingly undifferentiated regions of the plasma membrane. The basis of this proposal is to extend these particle tracking and manipulation experiments on several different fronts.
In Specific Aim I, the physical characteristics and nature of zones confining membrane proteins and lipids to small domains is investigated.
In Specific Aim II, experiments are proposed to assess whether this novel microstructure in the plane of the membrane is under explicit physiological control mediated in some cases by signal transduction pathways.
In Specific Aim III, a new method of probing barriers to diffusion at multiple points on the cell simultaneously is proposed employing magnetic fields to move or """"""""magnetophorese"""""""" particles attached to membrane components. Because this new information will alter the way we think about membrane structure and function, it is vital that we know all we can about the influence of the particle on these measurements; this is the goal of Specific Aim IV.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM041402-13
Application #
6342828
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Chin, Jean
Project Start
1988-12-01
Project End
2001-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
13
Fiscal Year
2001
Total Cost
$193,010
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Liu, Ping; Ridilla, Marc; Patel, Pratik et al. (2017) Beyond attachment: Roles of DC-SIGN in dengue virus infection. Traffic 18:218-231
Liu, Ping; Weinreb, Violetta; Ridilla, Marc et al. (2017) Rapid, directed transport of DC-SIGN clusters in the plasma membrane. Sci Adv 3:eaao1616
Jacobson, Ken; Liu, Ping (2016) Complexity Revealed: A Hierarchy of Clustered Membrane Proteins. Biophys J 111:1-2
Garcia-Parajo, Maria F; Cambi, Alessandra; Torreno-Pina, Juan A et al. (2014) Nanoclustering as a dominant feature of plasma membrane organization. J Cell Sci 127:4995-5005
Itano, Michelle S; Graus, Matthew S; Pehlke, Carolyn et al. (2014) Super-resolution imaging of C-type lectin spatial rearrangement within the dendritic cell plasma membrane at fungal microbe contact sites. Front Phys 2:
Liu, Ping; Wang, Xiang; Itano, Michelle S et al. (2014) Low copy numbers of DC-SIGN in cell membrane microdomains: implications for structure and function. Traffic 15:179-96
Liu, Ping; Wang, Xiang; Itano, Michelle S et al. (2012) The formation and stability of DC-SIGN microdomains require its extracellular moiety. Traffic 13:715-26
Navaratnarajah, Punya; Steele, Bridgett L; Redinbo, Matthew R et al. (2012) Rifampicin-independent interactions between the pregnane X receptor ligand binding domain and peptide fragments of coactivator and corepressor proteins. Biochemistry 51:19-31
Thompson, Nancy L; Navaratnarajah, Punya; Wang, Xiang (2011) Measuring surface binding thermodynamics and kinetics by using total internal reflection with fluorescence correlation spectroscopy: practical considerations. J Phys Chem B 115:120-31
Neumann, Aaron K; Itano, Michelle S; Jacobson, Ken (2010) Understanding lipid rafts and other related membrane domains. F1000 Biol Rep 2:31

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