1. Biological Membranes 薛雅薇 中央大學物理系

2. Cell Membrane

3. Two primary building blocks : - Protein - Lipid, or fat. Lipids form a bilayer. The glycocalyx carbohydrate network on the outside surface: - responsible for cell–cell recognition and adhesion to other cells. Membrane Structure (I)

4. 1. Supporting and retaining the cytoplasm (inner cell) 2. Being a selective barrier: Get nutrients in and waste products out. non-polar molecules and some small polar molecules can cross. Most polar compounds, e.g. amino acids, must be specifically transported across the membrane by proteins (Transport). Functions of cell membranes 4. Recognition 3. Communication (signaling, via receptors) Information Flow Through the Plasma Membrane via a Membrane Receptor Structure and function are related.

5. Structure of Lipid Molecule Lipid molecule contains both hydrophilic and hydrophobic regions. Polar headgroup : hydrophilic (i.e. water-loving) Tail (or acyl chain): hydrophobic (i.e. water-fearing) polar non-polar H 2 C H 2 C H 2 C H 2 C CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 H 2 C H 2 C H 2 C H 2 C H 2 C H 2 C H 2 C O O = C H C O H C H O CH 2 O ¯ P = O O–CH 2 – 2 –N + (CH 3 ) 3 CH 2 2 2 3 H 2 C H 2 C H 2 C H 2 C C = O CH 2 2 2

6. 60:40 DPPC/Chol bilayers Lipid motion: - Lateral - Rotational - nodding - … In liquid crystalline phase

7. Lipid rafts are postulated to be very important in signal transduction in cells (as signaling platforms, for example). Consists of specialized domains of different compositions and properties. These specialized domains (called lipid rafts) are enriched in cholesterol ( 膽固醇 ) and sphingolipids (high melting lipids) Size of domain: 0 – 10  m Membrane Structure (II) It has found that many diseases, such as Alzheimer's, Huntington's, Parkinson's disease, AIDS..etc are related to lipid rafts.

8. Fluorescence image (1:1 brainPC/brainSPM)+25mol%Chol Crane & Tamm 2004 Kruijff et al. 2001 AFM images (1:1 DOPC/SPM)+25mol%Chol Two bilayer thicknesses

9. Nuclear magnetic resonance (NMR, 核磁共振 ) Differential scanning calorimetry (DSC) Fluorescence microscopy Atomic force microscopy (AFM, 原子力顯微鏡 ) Probing Membrane’s structure & dynamics Use model membranes

10. Principles of NMR (Nuclear Magnetic Resonance) H 0 : Static Magnetic Field H 1 (t): Alternating Field with frequency  For a bare spin in the presence of H 0 : H zeeman =   n  H 0 I E m =   n  H 0 m For 2 H nuclear spin, I = 1 m =  1 0 1    =  E,  resonance occurs (absorption of energy)  LL m =  1 0 1 LL For a spin in the membranes info: local environments, mol. dynamics H = H zeeman + H Q

11. Solid-state NMR spectrometer ( 固態核磁共振儀 )

12. - Probing specific site by choosing proper  L - Sample in any form - Non-invasive Multi-component lipid mixtures, with one lipid labeled

13. ld lo Characteristic 2 H NMR spectra for liquid phases Liquid-disordered (disordered chain) Liquid-ordered (highly ordered chain) Cholesterol-associated Chemical composition, fraction of each domain, lipid-lipid & lipid-protein interactions, dynamics, mechanical properties …

14. gel + ld gel ld Pure POPE-d31 Probing phase transition Lattice melting & chain melting

15. Thank You