1. BIO307- Bioengineering principles SPRING 2019
Lecture 3
Cellular Principles
Lecturer: Jasmin Sutkovic

2. Content Cell structure and function Extracellular matrix
Molecules in the cell membrane
Cell proliferation
Stem cells
Cell death
Cell culture and technology

3. The cell

4. Cell culture and function
For example, all cells are surrounded by a lipid bilayer membrane, which separates the intracellular space from the extracellular space.
This plasma membrane restricts the movement of water and ions into and out of the cell.
Cells can be divided into two main classes: prokaryotic and eukaryotic

5. Prokaryotic cells
Prokaryotic cells (e.g., bacteria, cyanobacteria, archaebacteria) are simple, lacking a nucleus, cytoplasmic organelles, and a cytoskeleton. These cells maintain their shape because of the presence of a rigid cell wall.
In bacteria, the cell wall is composed of peptidoglycan, a polysaccharide polymer that is cross-linked by amino acids for additional stability.
Gram-positive bacteria have a predominantly peptidoglycan wall, whereas Gram-negative bacteria have two walls: a thinner inner wall, containing peptidoglycan, and an outer lipopolysaccharide layer.

8. Tissues
Within the body, a collection of cells of a similar type is called a tissue.
There are four general types of tissues: muscle, nervous, epithelial, and connective tissues
An organ is a collection of two or more primary tissues, which are organized into a functional unit. Some organs contain all four tissue types, for example stomach
Muscle tissue is specialized for movement; the cells within muscle tissue are rich in specialized proteins (described in Box 4.1) that enable the cells to contract. Nervous tissue is capable of initiating signals and transmitting them from cell to cell, in a coordinated fashion. Epithelial tissues are organized into sheets that cover body surfaces: They separate the body from its environment (skin and intestinal epithelium) and they line glands to enable regional secretion of specialized fluids. Connective tissue is rich in extracellular material that provides mechanical strength and anchors adjacent tissues. All of the various types of circulating blood cells are considered to be specialized forms of connective tissues. An organ is a collection of two or more primary tissues, which are organized into a functional unit. Some organs contain all four tissue types; for example, the stomach has an epithelial lining, a muscular layer for mixing of stomach contents, a nervous tissue for coordination of muscular action, and a connective tissue for binding the other tissues into a unit.

9. ECM
Extra cellular - protein fibers and filaments, which are embedded in a hydrated gel of high-molecular-weight, carbohydrate-rich molecules
The specialized molecules of the ECM are predominantly of three classes: proteins, glycosaminoglycans (GAGs), and proteoglycans

10. Structural proteins include collagen and elastin.
The hydrated gel is composed of GAGs, which are unbranched polysaccharide chains.
Most GAGs are covalently attached to a protein core to form proteoglycans.
There are two categories of proteins in the ECM: structural and adhesive.
Structural proteins include collagen and elastin.
Collagen provides strength whereas elastin provides elasticity
Elastin is particularly abundant in certain tissues in which stretch and recovery are important for their function, such as the vessel wall of aorta.
The specialized molecules of the ECM are predominantly of three classes: proteins, glycosaminoglycans (GAGs), and proteoglycans.

11. Other proteins..
Other adhesive proteins such as fibronectin and laminin help to bind the other matrix components together and facilitate attachment of cells to the ECM.

13. Molecules in the cell membrane
The plasma membrane, is a phospholipid bilayer that supports a wealth of embedded and coupled membrane proteins..
All cells in the human body require proteins to facilitate and regulate the transport of molecules in and out of the cell
For example: how glucose enters the cell?

14. Biomedical engineers now incorporate these specialized molecules into devices, such as biosensors, that exploit the biological properties of recognition and selective transport of these molecules.

15. Membrane proteins that regulate the transport
Many molecules do not diffuse through lipid bilayers.
Polar molecules—such as sugars, ions, and most amino acids—are not able to dissolve easily into the lipid-rich inner region of the bilayer
FACILITATED TRANSPORT IS DONE THROUGH THE HELP OF OTHER PROTEIN TRANSPORTERS

16. Example for Glucose
Facilitated proteins that transfer the glucose are limited, mainly they enter the cell through aqous pathways through the hydrophobic bilayers.
The glucose transporter facilitates glucose permeation by periodic changes in conformation:
In one conformation, a glucose binding site is exposed on the extracellular face, whereas in another conformation, the binding site is exposed to the intracellular face

17. ACTIVE TRANSPORT
Compared to passive transport, here energy on form of ATP is provided.
The Na+/K+-ATPase pump is the most well-characterized active transport system
It pumps sodium out of cells while pumping potassium into cells, both against their concentration gradients !!!

18. ION TRANSPORT, MEMBRANE POTENTIALS, AND ACTION POTENTIALS
Some ion channels are selective, permitting the permeation of only specific ions, such as Na+, K+, or Cl−. Selectivity is accomplished by a combination of channel characteristics including molecular sieving (which selects for ions of certain size), binding to the protein surface, and stabilization of the nonhydrated ion. Some channels are gated; gated channels exist in multiple states that either permit or exclude ion movement across the membrane. In the open state, conductance (or permeability) to the ion rapidly increases. The closed/open state of the ion channel is regulated by extracellular and intracellular conditions. Some channels are voltage-regulated; others are regulated by binding of a chemical ligand or mechanical stretching of the membrane.
ION TRANSPORT

20. RECEPTOR-MEDIATED ENDOCYTOSIS AND SIGNALING
Is anmechanism in which specific molecules are ingested into the cell.
The specificity results from a receptor-ligand interaction.
Receptors on the plasma membrane of the target tissue will specifically bind to ligands on the outside of the cell.
An endocytotic process occurs and the ligand is ingested.

22. Control of cell cycle
We can illustrate the importance of an adjustable cell-cycle control system  by extending our washing machine analogy. The control system of simple embryonic cell cycles, like the controller in a simple washing machine, is based on a clock. 
The clock is unaffected by the events it regulates and will progress through the whole sequence of events even if one of those events has not been successfully completed

23. But three checkpoints exists..

24. For example, certain cell proteins appear to function as biological clocks that encode an internal program for timed cell fate.
They inhibit or support the cell cycle.
Signals from the cell’s external environment are also known to be critical in the decision-making process
Diffusible protein growth factors, such as EGF or vascular endothelial cell growth factor (VEGF), can bind to receptors on the cell membrane and trigger signaling cascades inside the cell that eventually lead to increased expression of growth-promoting genes.

25. CDks
At the heart of the cell-cycle control system  is a family of protein kinases known as cyclin-dependent kinases (Cdks).
The activity of these kinases rises and falls as the cell progresses through the cycle.
Cyclical changes in Cdk activity are controlled by a complex array of enzymes and other proteins

26. Stem cells and Cell differentiation
Stem cells are unspecialized precursor cells that are capable of differentiating or changing into more specialized cell types.
Stem cells are capable of self renewal.
Stem cells differentiate in all other cells
Stem cells have the capacity to populate tissues as functional cells after transplantation into a recipient.
Topic for project: Stem cells- recent developments !

27. Types of stem cells
Stem cells are classified with respect to the age at which they are isolated.
Pluripotent stem cells. These possess the capacity to divide for long periods and retain their ability to make all cell types within the organism
Fetal stem cells. These are obtained from tissues of a developing human fetus. These cells have some characteristics of the tissues they are taken from
Adult stem cells. These are obtained from some tissues of the adult body. The most commonly used example is the bone marrow.
Unipotent cells can produce only one cell type, their own,[4] but have the property of self-renewal, which distinguishes them from non-stem cells (e.g. progenitor cells, which cannot self-renew).

28. Cell Death There are two types of cell death: necrosis and apoptosis
Cells that die because of tissue damage undergo necrosis; the cells swell and burst, releasing their contents and often triggering an inflammatory response.
In contrast, apoptosis, often referred to as programmed cell death, follows a sequence of steps in which the chromatin condenses, the cell shrinks, and the plasma membrane pinches off to form apoptotic bodies.
These apoptotic bodies are then phagocytosed or engulfed by specialized cells of the immune system called macrophages.

29. Cell death
Apoptosis VS necrosis

30. Cell culture technology
Culture techniques can be used to produce many more cells or to produce cell-related products such as proteins, DNA, Bacteria or viruses.
The biotechnology industry is based on cell culture