细胞生物.1 | Plasma Membrane (PM)

Plasma Membrane (PM) 质膜

General Properties 一般特性

Encloses each cell and defines its boundaries
包围每个细胞并界定其边界
Semipermeable, fluid, never has a free edge
半透性、流动性，不存在自由边缘
Asymmetric
不对称性

Composition 组成

Phospholipids 磷脂（形成基本骨架）
- Include sterols like cholesterol 含有固醇类如胆固醇
- Inside and outside layers are sealed to prevent entry of water-soluble molecules
  内外层封闭，防止水溶性分子进入
Proteins 蛋白质 – make up about half of the membrane
占膜成分约一半
Carbohydrates 碳水化合物 – only a small portion
占比例很小
- Exist as glycoproteins and glycolipids
  以糖蛋白和糖脂形式存在

Lipid Mobility in Membrane 膜脂的运动方式

Rotation 旋转（分子自身旋转）
Lateral diffusion 侧向扩散（在膜平面上横向移动）
Flip-flop 翻转（罕见，跨内外层移动）
Flexion 弯曲（脂肪酸链弯曲）

Factors Affecting Fluidity 影响流动性的因素

Fatty acid tail length 脂肪酸链长（越短 = 越流动）
Saturation 饱和度（不饱和 = 越流动）
Temperature 温度（越高 = 越流动）
Cholesterol 胆固醇（增加稳定性）
Protein content 蛋白质含量（越多 = 越刚性）

Plasma Membrane Asymmetry 质膜不对称性

1. Lipids 脂质

Different phospholipids are distributed asymmetrically:
不同磷脂分布不均：
- Outer layer 外层: SM（鞘磷脂）, PC（磷脂酰胆碱）
- Inner layer 内层: PS（磷脂酰丝氨酸）, PE（磷脂酰乙醇胺）, PI（磷脂酰肌醇）

2. Proteins 蛋白质

Some proteins face only the inside or only the outside
有些蛋白质仅朝向内侧或外侧
Glycolipids (5% of PM) face outside
糖脂（约占膜 5%）朝向外侧

3. Carbohydrates 碳水化合物

Exist only on the outer layer
仅存在于外层

→ Due to asymmetry, membrane potential and ion concentrations differ between inside and outside
→ 由于不对称性，膜内外的膜电位和离子浓度不同

Glycolipids 糖脂

Bond with each other via hydrogen bonds
通过氢键相互结合
Functions 功能:
1. Protection (physical and chemical) 保护（物理和化学）
2. Electrical effects (e.g., calcium signaling) 电学效应（如钙信号）
3. Myelin – insulation 髓鞘作用（绝缘）
4. Receptor functions 受体功能
5. Cell-cell interactions 细胞间相互作用

Glycocalyx (Cell Coat) 糖萼（细胞外被）

Composed of proteins + sugars on outer layer of PM
由蛋白质和糖组成，位于质膜外层
Rich in carbohydrates 富含碳水化合物
Includes 包括：
1. Glycolipids 糖脂
2. Glycoproteins (membrane-bound & secreted) 糖蛋白（膜结合型和分泌型）
3. Proteoglycans 蛋白聚糖
Functions 功能:
1. Protection (mechanical/chemical) 保护（机械和化学）
2. Cell-cell interaction or repulsion 细胞间相互作用或排斥

PM Proteins 质膜蛋白质

Functions 功能:

Receptors 受体
Channels 通道
Photosynthesis 光合作用
Electron transport (respiration) 电子传递（呼吸作用）
Structural support 结构支撑
Enzymes 酶作用

3 Classes of Membrane Proteins 膜蛋白的三类

1. Transmembrane (Integral) 跨膜（整合）蛋白

Make up 27–30% of all proteins 占全部蛋白质 27–30%
Amphipathic 两亲性（既有亲水又有疏水区）
Two main types 两种主要类型:
a. α-Helix α-螺旋
- Can be single or multi-pass 可单跨或多跨
- Backbone = hydrophilic 骨架=亲水
- Side chains = hydrophobic 侧链=疏水
  b. β-Barrels β-桶
- Found in mitochondria, not in PM 存在于线粒体，不在质膜
- Inside = hydrophilic 内部亲水
- Outside = hydrophobic 外部疏水
Can move laterally within the membrane 可在膜内侧向移动

2. Lipid-Linked Proteins 脂质锚定蛋白

Covalently bonded to lipids 与脂质共价结合
Function: adhesion 功能：黏附
Classes 类别:
1. GPI-anchored proteins (extracellular side) GPI锚定蛋白（胞外侧）
2. Proteins bound to prenyl groups (cytosolic side, e.g., Ras signaling) 与异戊二烯基结合的蛋白（胞质侧，如Ras信号）
3. Proteins bound to fatty acids (cytosolic side) 与脂肪酸结合的蛋白（胞质侧）

3. Peripheral Proteins 外周蛋白

Attached by non-covalent electrostatic interactions 通过非共价静电作用附着
Functions 功能:
1. Cell-cell communication 细胞间通讯
2. Part of cytoskeleton 细胞骨架的一部分
Not always tightly bound 并非总是紧密结合

Mobility of Lipids & Proteins in Bilayer 脂质与蛋白质在双层膜中的运动

Both lipids and proteins move via lateral diffusion
脂质和蛋白质都可以通过侧向扩散运动

Experiment 1: Heterokaryon Fusion 实验1：异核细胞融合（人+鼠细胞）

Observation 观察: Proteins mixed over time 蛋白质随时间混合
Conclusion 结论:
1. Membrane proteins are mobile 膜蛋白可移动
2. Temperature affects mobility 温度影响流动性
3. Fluidity matters 流动性是关键

Experiment 2: FRAP (Fluorescence Recovery After Photobleaching) 实验2：光漂白后荧光恢复

Label membrane with fluorescent tags
用荧光标记膜
Bleach a spot 光漂白一处区域
Watch fluorescence return 观察荧光恢复
Conclusion 结论:
1. Proteins are mobile 蛋白质具有流动性
2. Movement limited by structures 运动受结构限制
3. Type of protein matters 蛋白质种类会影响运动

Fluid Mosaic Model 流动镶嵌模型

Still valid 依然适用
Membrane proteins are dynamic, not static
膜蛋白是动态的，而非静止
Asymmetry is maintained 保持不对称性

Lipid Rafts 脂筏

Thicker, more ordered regions of the membrane
膜中较厚且排列更有序的区域
Enriched in cholesterol and sphingolipids
富含胆固醇和鞘脂类
Float within the membrane
漂浮在膜中
Often contain GPI-anchored signaling proteins
常含有 GPI 锚定的信号蛋白

Red Blood Cell (RBC) Plasma Membrane 红细胞质膜

No nucleus or organelles
无细胞核和细胞器
Shape and stability depend entirely on PM and underlying cytoskeleton
形态和稳定性完全依赖质膜及下方的细胞骨架
Key transmembrane proteins 主要跨膜蛋白:
- Band 3
- Glycophorin
Cytoskeleton 细胞骨架: spectrin 血影蛋白
Structural proteins 结构蛋白:
- Fibrous 纤维状: 长条形，支撑作用
- Globular 球状: 紧凑，更常见

Three Classes of Membrane Proteins（膜蛋白的三大类）

1. Transmembrane Proteins (Integral Proteins)

跨膜蛋白 / 整合蛋白

These proteins span across the entire lipid bilayer. They are amphipathic—meaning part of them is hydrophilic (water-loving) and part hydrophobic (water-repelling), just like phospholipids.

Structure:

Most common structure is the α-helix, which can cross the membrane once or multiple times.
Another type is the β-barrel, found in mitochondria membranes, not in the plasma membrane.

中文解释：
跨膜蛋白是穿透整个脂双层的蛋白，它们既有亲水区域也有疏水区域。最典型的结构是α螺旋，像一根穿过细胞膜的螺旋管。

Functions:

Receptors – receive signals from outside the cell (e.g., hormones, neurotransmitters)
Channels – allow specific ions or molecules to pass through
Photosynthesis / Electron transfer – involved in energy-related pathways like respiration

2. Lipid-Anchored Proteins (Covalently Bound to Lipids)

脂锚定蛋白 / 共价连接脂质的蛋白

These are not embedded in the membrane, but are covalently attached to lipid molecules that are inserted into the bilayer.

中文解释：
这类蛋白没有直接插入膜里，而是通过一段脂肪链“锚定”在膜上。像是绑在小船上的锚一样，蛋白被固定在脂双层表面。

Types:

GPI-anchored (outer leaflet)
Prenylated proteins or proteins bound to fatty acids (inner leaflet)

Functions:

Receptors (same as above)
Enzymes – catalyze specific reactions at the membrane surface

Adhesion – involved in sticking cells to each other or the extracellular matrix

3. Peripheral Proteins

周边蛋白 / 外围蛋白

These proteins are not embedded in the membrane. They attach via non-covalent interactions (electrostatic or hydrogen bonds) with membrane lipids or other proteins.

中文解释：
外围蛋白只是“吸附”在膜的一侧，可以是细胞质面也可以是外侧，不深入膜内。它们通过静电作用或氢键与膜结合，结合较弱，容易脱落。

Functions:

Structural support – help maintain the shape of the cell, often by linking to the cytoskeleton
Enzymes – work on the inner or outer surface of the membrane

Cell-to-cell communication – allow cells to recognize and interact with each other

如果你要记住这三类，建议配套记住：

是否深入膜内（transmembrane深入双层，lipid-anchored绑在脂链上，peripheral靠在边上）
关键功能关键词：
- Transmembrane = receptor, channel, transfer
- Lipid-anchored = enzyme, adhesion
- Peripheral = structure, signal, enzyme

Lipid Movement Types（脂质在膜中的移动类型）

细胞膜虽然稳定，但其实是非常动态的结构。膜中的脂质（主要是磷脂）并不是静止的，它们会以不同方式在膜中移动，维持膜的**流动性（fluidity）**和功能。

1. Rotation / Spin（自转）

Lipids rotate around their long axis, like a spinning top.

中文解释：
磷脂分子绕着自己的“尾巴”方向旋转，好比在原地打转。这是最常见、最快速的运动方式之一。

2. Lateral Diffusion / Shift（横向扩散 / 平移）

Lipids move sideways within the same monolayer of the bilayer.

中文解释：
脂质可以在膜的同一层内（内层或外层）横向平移，像是你在人群中侧身移动。这种运动非常频繁，是维持膜流动性的核心机制。

3. Flip-Flop（翻转层，罕见）

A lipid moves from one monolayer to the other—outer to inner or inner to outer.
This requires enzymes called flippases, floppases, or scramblases.

中文解释：
这是脂质从膜的一侧“翻”到另一侧，比如从外层翻到内层。这种移动很罕见，因为要穿越疏水核心，很不容易。一般需要酶帮助完成，比如flippase（负责向内翻）、floppase（向外翻）、scramblase（无方向翻转）。

4. Flexion（尾部弯曲）

Movement of fatty acid tails—the tails wiggle or bend back and forth.

中文解释：
脂肪酸尾巴自己扭来扭去的动作，不是整分子动，而是局部的“抖动”。这种微小动作有助于维持膜的柔软性。

总结 Summary

Movement Type	Description (英文)	中文解释	频率
Rotation	Lipid spins around its own axis	原地自转	高
Lateral diffusion	Lipid shifts sideways in the same monolayer	在同一层中横向移动	高
Flip-flop	Lipid jumps between inner and outer layers (rare)	脂质翻转到另一层（需要酶）	低
Flexion	Fatty acid tails wiggle or bend	尾巴摆动	中

Membrane Asymmetry（膜的结构不对称性）

Why is the membrane asymmetric?

Because the two leaflets (layers) of the lipid bilayer are different—in composition, orientation, and function.

中文解释：
膜的两层结构在组成和功能上都有区别，这种不对称性是细胞生存和功能调控的基础。

Key Features of Asymmetry

1. Different phospholipids on each side

Outer layer: SM (Sphingomyelin), PC (Phosphatidylcholine)
Inner layer: PS (Phosphatidylserine), PE (Phosphatidylethanolamine), PI (Phosphatidylinositol)

中文提示：
外层偏中性，内层带负电（比如PS），这和细胞信号、凋亡有关。

2. Carbohydrates only on the outside

Function in recognition (e.g. immune response) and protection (e.g. mechanical/chemical stress)
Attached to either glycoproteins or glycolipids

中文解释：
糖类只存在于膜的外侧，常用于识别（比如血型）和保护（例如形成糖衣层 glycocalyx）。

3. Some proteins only face inside or outside

This affects signal reception, anchoring, and molecular transport
Example: certain receptor domains always face extracellular space

Functional Importance of Asymmetry（功能上的重要性）

If PS flips to the outer layer (e.g. during apoptosis), it signals immune cells to destroy the cell
→ “PS outside = cell is dying”
→ Leads to apoptosis, then phagocytosis

中文解释：
PS正常只在内侧，如果它被翻到外侧，就相当于贴了“我要死了”的标签，免疫系统会来吞噬它。

Experimental Evidence

🧪 Red Blood Cell Hemolysis Experiment

Expose RBCs to different salt concentrations → cells burst
Membranes fragment → form vesicles
These vesicles have inside-out or right-side-out orientation
Enzymes like phospholipase are used to probe which leaflet faces out
Confirms asymmetry of lipid/protein layout

中文解释：
实验通过改变红细胞的渗透压让它破裂，形成膜囊泡（向外或向内的囊泡），再用酶来分析哪一层朝外，验证了膜的结构是有方向性的。

Carbohydrates on Membranes

Function via glycolipids and glycoproteins:

Protection
Electrical effects (e.g. charge, ion balance)
Insulation in myelin
Receptors
Cell interactions

中文提示：
糖类不仅保护膜，还参与电荷平衡、髓鞘绝缘、受体识别等，是多面手。

Phospholipid Bilayer（磷脂双分子层）

Basic Structure

Phospholipids are the building blocks of the cell membrane.
Each phospholipid molecule has two main parts:

Hydrophilic head（水溶性头部）
- Loves water
- Made of a phosphate group
- Faces toward the water (extracellular fluid or cytosol)
Hydrophobic tails（疏水性尾部）
- Hate water
- Made of fatty acid chains
- Face away from the water, hide inside the membrane

中文解释：
磷脂像个“汤匙”结构，勺子头是亲水的（能和水相处），尾巴是疏水的（讨厌水）。
两个磷脂一上一下排列，亲水头朝外，疏水尾藏在中间，自动排成双层结构。

Shape & Arrangement

In water, phospholipids self-assemble into a bilayer.
This is the most stable arrangement because:
- Heads can interact with water
- Tails avoid water by facing inward
This forms a fluid yet stable membrane:
- Flexible like oil
- But also forms a solid barrier against most water-soluble substances

Why Bilayer Instead of Single Layer?

A single layer would expose hydrophobic tails to water → unstable
A bilayer hides tails inside and lets both surfaces stay hydrophilic
This creates a selectively permeable barrier—some molecules can pass, others can’t

中文理解：
双层膜结构就像三明治，亲水头是面包片，疏水尾是夹心肉，夹心不能见水，所以必须夹在中间。这样才能保护细胞不被水溶性物质随意穿透。

Bonus Tip: In a cross-section, the membrane looks like this:

Water (outside cell)
↑
[ Hydrophilic heads ]
[ Hydrophobic tails ]
[ Hydrophobic tails ]
[ Hydrophilic heads ]
↓
Water (inside cell)