1.3.3 33BTransport Mechanisms Across Cell Membranes
An important function of a biological membrane is to serve as a barrier to the outside
world; it prevents items from coming into the cell and prevents the cell interior from leaking out
of the cell. However, membranes are not impenetrable walls. Obviously, nutrients must enter the
cell and waste products have to leave in order for the cell to survive. For this and many other
reasons, it is crucial that membranes be selectively permeable. For example, the movement of
ions across membranes is important in regulating vital cell characteristics such as cellular pH and
osmotic pressure. Membrane permeability is also a key determinant in the effectiveness of drug
absorption, distribution, and elimination. A membrane permits small hydrophobic molecules to
readily pass back and forth across the membrane (lipids) but presents a formidable barrier to
larger and more hydrophilic molecules (such as ions). These substances must be transported
across the membrane by special proteins. We will look briefly at the three major ways that both
15
small hydrophobic molecules and hydrophilic molecules (such as ions) cross the barriers
presented by cell membranes.
1.3.3.1 40BDiffusion Across the Lipid Bilayers
Since membranes are held together by weak forces, certain molecules can slip between
the lipids in the bilayer and cross from one side to the other. This spontaneous process is termed
diffusional bilayer crossing (Fig.1-7). This process allows molecules that are small and lipophilic
(lipid-soluble), including small uncharged polar molecules such as water, urea, carbon dioxide,
methanol, dimethylsulfoxide, glycerol, ethanol and non-polar molecules such as oxygen,
nitrogen and most drugs rapidly penetrate through the bilayer [22]. This diffusion through the
bilayer is a passive diffusion process where no energy is involved and substances are moved
down the concentration gradient (Fick’s Law). The rate of diffusion is increased by increasing
the concentration difference, the surface area and membrane permeability. Lipid bilayers are
much less permeable to larger polar molecules, and are virtually impermeable to ions, which are
surrounded by a cage of water.
1.3.3.2 41BProtein-Mediated Transport
In order to cross the hydrophobic interior of the bilayer, water-soluble molecules (those
that are either charged or have polar groups) and large molecules require the action of membrane
transport proteins. These integral membrane proteins provide a continuous protein-lined pathway
through the bilayer. There are two classes of membrane transport proteins that we will discuss:
carrier proteins, which literally carry specific molecules across, and channel proteins, which
form a narrow pore through which ions can pass (Fig. 1-7). Channel proteins carry out passive
transport [23], in which ions travel spontaneously down their gradients. Some carrier proteins
mediate passive transport (also called facilitated diffusion), while others can be coupled to a
source of energy to carry out active transport, in which a molecule is transported against its
concentration gradient (Fig. 1-7).
1.3.3.3 42BEndocytosis/ Exocytosis
Large macromolecules (e.g., proteins, viruses, lipoprotein particles) require more
complex mechanisms to traverse membranes, and are transported into and out of cells selectively
via endocytosis and exocytosis (secretion). Interestingly, endocytosis and exocytosis are not only
important for the import/export of large molecules. Often, essential small molecules that are
hydrophobic or toxic (e.g., iron) travel through the bloodstream bound to proteins, which enter
and exit cells via these mechanisms.
Although water is a polar molecule it has an unusual behavior, it can cross the bilayer
rapidly, passing through a phospholipid bilayer in about a millisecond. Water molecules also
move more rapidly through phospholipids bilayer than do substances that are dissolved in it.
Water molecules move through the membranes at about 105 times faster than that of glucose
molecules and 1010 times faster than that that of Na+ and K+ ions. We can get an idea of just
17
how fast water can pass across membranes into cells by watching how quickly red blood cells
burst when put into water, or by noticing how quickly the leaves of a wilting plant regain their
stiffness when placed in a vase of water. The reasons for this rapid movement of water might be
because of its small size, its abundant concentration contents, and its dipolar nature which helps
it to cross the charged lipid head group region. Though the exact reason is not known water does
dissolve to a very slight extent in the hydrophobic core region. This helps us to make a
hypothesis that a change in water concentration on one side of the bilayer should result in a rapid
flow of water across the membrane.
1.3.4 34BCryoprotectants
A cryoprotectant is a substance that is used to protect biological tissue from cell damage
during freezing and thawing processes. It is extremely rare for cells to survive freezing and
thawing without the presence of some type of cryoprotective agents (CPAs). Some
cryoprotectants function by lowering a solution's or a material's glass transition temperature. In
this way, the cryoprotectants prevent actual freezing, and the solution maintains some flexibility
in a glassy phase. Many cryoprotectants also function by forming hydrogen bonds with
biological molecules as water molecules are displaced. Hydrogen bonding in aqueous solutions
is important for proper protein and DNA function. Thus, as the cryoprotectant replaces the water
molecules, the biological material retains its native physiological structure (and function),
although they are no longer immersed in an aqueous environment. This preservation strategy is
most often observed in anhydrobiosis. Some of the common cryoprotective agents used are
dimethylsulfoxide (DMSO), ethylene glycol, glycerol, propylene glycol, sucrose and trehalose.
Glycerol and dimethylsulfoxide have been used for decades by cryobiologists to reduce ice
formation in cells that are cold-preserved in liquid nitrogen. In most cases these compounds must
penetrate through the cell membrane in order to exert their protective effect. Passive transport of
water and cryoprotective solutes across the membranes of individual cells plays an absolutely
important role in low temperature biology (cryopreservation), since low temperatures tend to
diminish the relative importance of active transport processes. So cryopreservation requires an
understanding of passive transport of cryoprotectant and water across the cell membrane. Due to
the wide use of DMSO as cryoprotectant, in this study we have primarily focused on the passive
transport of water and DMSO across the cell membrane
1.3.3 33BTransport กลไกผ่านเยื่อหุ้มเซลล์ฟังก์ชันสำคัญของเมมเบรนชีวภาพจะเป็นอุปสรรคภายนอกโลก ป้องกันสินค้าไม่ให้เข้ามาในเซลล์ และป้องกันไม่ให้รั่วไหลออกภายในเซลล์ของเซลล์ อย่างไรก็ตาม เยื่อหุ้มได้ไม่ impenetrable กำแพง อย่างชัดเจน สารอาหารที่ต้องการเซลล์และของเสียจะต้องปล่อยให้เซลล์เพื่อความอยู่รอด นี้และหลายอื่น ๆเหตุผล มันเป็นสิ่งสำคัญที่เยื่อหุ้มจะเลือก permeable ตัวอย่าง การเคลื่อนที่ของประจุในสารเป็นสิ่งสำคัญในการควบคุมลักษณะเซลล์สำคัญเช่นเซลลูลาร์ pH และความดันออสโมติก Permeability ของเมมเบรนเป็นดีเทอร์มิแนนต์สำคัญในประสิทธิภาพของยาดูดซึม การกระจาย และตัดออก เมมเบรนอนุญาตให้โมเลกุล hydrophobic เล็กไปพร้อมผ่านไปมาในเมมเบรน (โครงการ) แต่นำเสนออุปสรรคอันตรายถึงชีวิตใหญ่ และ hydrophilic มากโมเลกุล (เช่นกัน) ต้องลำเลียงสารเหล่านี้ผ่านเมมเบรนโดยโปรตีนพิเศษ เราจะดูสั้น ๆ วิธีหลักสามวิธีที่ทั้ง 15hydrophobic โมเลกุลเล็กและโมเลกุล hydrophilic (เช่นกัน) ข้ามอุปสรรคนำเสนอ โดยเยื่อหุ้มเซลล์1.3.3.1 40BDiffusion ข้าม Bilayers ไขมันตั้งแต่เข้าขึ้นร่วมกัน โดยกองทัพอ่อนแอ โมเลกุลบางอย่างสามารถจัดส่งระหว่างโครงการใน bilayer และข้ามจากด้านหนึ่งไปยังอีก เรียกว่ากระบวนการนี้อยู่diffusional bilayer crossing (Fig.1-7). This process allows molecules that are small and lipophilic(lipid-soluble), including small uncharged polar molecules such as water, urea, carbon dioxide,methanol, dimethylsulfoxide, glycerol, ethanol and non-polar molecules such as oxygen,nitrogen and most drugs rapidly penetrate through the bilayer [22]. This diffusion through thebilayer is a passive diffusion process where no energy is involved and substances are moveddown the concentration gradient (Fick’s Law). The rate of diffusion is increased by increasingthe concentration difference, the surface area and membrane permeability. Lipid bilayers aremuch less permeable to larger polar molecules, and are virtually impermeable to ions, which aresurrounded by a cage of water.1.3.3.2 41BProtein-Mediated TransportIn order to cross the hydrophobic interior of the bilayer, water-soluble molecules (thosethat are either charged or have polar groups) and large molecules require the action of membranetransport proteins. These integral membrane proteins provide a continuous protein-lined pathwaythrough the bilayer. There are two classes of membrane transport proteins that we will discuss:carrier proteins, which literally carry specific molecules across, and channel proteins, whichform a narrow pore through which ions can pass (Fig. 1-7). Channel proteins carry out passivetransport [23], in which ions travel spontaneously down their gradients. Some carrier proteinsmediate passive transport (also called facilitated diffusion), while others can be coupled to a
source of energy to carry out active transport, in which a molecule is transported against its
concentration gradient (Fig. 1-7).
1.3.3.3 42BEndocytosis/ Exocytosis
Large macromolecules (e.g., proteins, viruses, lipoprotein particles) require more
complex mechanisms to traverse membranes, and are transported into and out of cells selectively
via endocytosis and exocytosis (secretion). Interestingly, endocytosis and exocytosis are not only
important for the import/export of large molecules. Often, essential small molecules that are
hydrophobic or toxic (e.g., iron) travel through the bloodstream bound to proteins, which enter
and exit cells via these mechanisms.
Although water is a polar molecule it has an unusual behavior, it can cross the bilayer
rapidly, passing through a phospholipid bilayer in about a millisecond. Water molecules also
move more rapidly through phospholipids bilayer than do substances that are dissolved in it.
Water molecules move through the membranes at about 105 times faster than that of glucose
molecules and 1010 times faster than that that of Na+ and K+ ions. We can get an idea of just
17
how fast water can pass across membranes into cells by watching how quickly red blood cells
burst when put into water, or by noticing how quickly the leaves of a wilting plant regain their
stiffness when placed in a vase of water. The reasons for this rapid movement of water might be
because of its small size, its abundant concentration contents, and its dipolar nature which helps
it to cross the charged lipid head group region. Though the exact reason is not known water does
dissolve to a very slight extent in the hydrophobic core region. This helps us to make a
hypothesis that a change in water concentration on one side of the bilayer should result in a rapid
flow of water across the membrane.
1.3.4 34BCryoprotectants
A cryoprotectant is a substance that is used to protect biological tissue from cell damage
during freezing and thawing processes. It is extremely rare for cells to survive freezing and
thawing without the presence of some type of cryoprotective agents (CPAs). Some
cryoprotectants function by lowering a solution's or a material's glass transition temperature. In
this way, the cryoprotectants prevent actual freezing, and the solution maintains some flexibility
in a glassy phase. Many cryoprotectants also function by forming hydrogen bonds with
biological molecules as water molecules are displaced. Hydrogen bonding in aqueous solutions
is important for proper protein and DNA function. Thus, as the cryoprotectant replaces the water
molecules, the biological material retains its native physiological structure (and function),
although they are no longer immersed in an aqueous environment. This preservation strategy is
most often observed in anhydrobiosis. Some of the common cryoprotective agents used are
dimethylsulfoxide (DMSO), ethylene glycol, glycerol, propylene glycol, sucrose and trehalose.
Glycerol and dimethylsulfoxide have been used for decades by cryobiologists to reduce ice
formation in cells that are cold-preserved in liquid nitrogen. In most cases these compounds must
penetrate through the cell membrane in order to exert their protective effect. Passive transport of
water and cryoprotective solutes across the membranes of individual cells plays an absolutely
important role in low temperature biology (cryopreservation), since low temperatures tend to
diminish the relative importance of active transport processes. So cryopreservation requires an
understanding of passive transport of cryoprotectant and water across the cell membrane. Due to
the wide use of DMSO as cryoprotectant, in this study we have primarily focused on the passive
transport of water and DMSO across the cell membrane
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