1. Cell Signaling and Tissue Engineering

2. Why Cell Signaling? Complex system of communication
Affects a cell’s ability to respond to its environment
Cell signaling affects:
Development
Tissue Repair
Immunity
Movement
Diseases
Cells must be able to interpret a large variety of signals that they receive from other cells in order to coordinate cellular behavior. Cell signaling affects a cell’s ability to respond to its environment, affecting activities such as development, tissue repair, and immunity. The cells ability to send these signals relies on a process called signal transduction, along with an assortment of different signaling pathways.

3. What Happens When Cells Miscommunicate??
Diabetes
Rheumatoid Arthritis
Cancer
Asthma
Lupus
Multiple Sclerosis
For example, if you think about diabetes
a disease characterized by the body’s inability to produce/use insulin (hormone) in order to maintain proper glucose levels in the body.
Something goes wrong with the cellular signaling and the pancreas does not get the message to secrete the necessary amounts of insulin when sugar levels are high

4. How Do Cells Send Signals?
There are five different types of signaling pathways:
Contact Dependent
Autocrine
Paracrine
Synaptic
Endocrine
Why does such a variety of signaling pathways exist?
Contact-dependent: Signaling cells contain a membrane bound signaling molecule. The target cell contains a receptor. When the cells come into direct contact with each other, the signal is passed over. This pathway is intimate and short-ranged.
Autocrine: Single cell diffuses signaling molecules which are self-recepted. This pathway is short-ranged.
Paracrine: Signaling molecules diffuse locally, therein by remaining close to the cell that secreted them. Signaling molecules are intercepted by signaling cell which diffuses signal for the target cells. This pathway usually acts between relatively short distances separating two cells.
Synaptic: A neuron sends electrical impulses down an axon. At axon terminal, electrical signals are converted to chemical signals (neurotransmitter). Chemical signals diffuse to reach target cell. Cell signal covers long distances; delivered quickly and specifically to target cells by axon.
Endocrine: An endocrine cell secretes a hormone signaling molecule into the bloodstream, which travels throughout the bloodstream until the target cell is reached. Cell signal covers long distances and is broadcast widely.

5. Three Stages to Extracellular Signaling
Ligand Binding
Ligand binding to receptor induces conformational change
Transduction
Amplification and spreading of signal down specific pathways in cell
Cellular Response
Cell response to signal
May result in any of the following:
Gene transcription
Cell proliferation/division
Cell survival
The Three Phases of Signal Response
Ligand Binding
Receptors have high affinities for ligands because they are often present in small amounts
When the ligand binds the receptor there is a conformational change in the receptors structure
Often, you need more than one ligand to activate one receptor
Signal Transduction
A reversible and fast step
There is an amplification and spreading of the signal generated by other factors travelling down specific pathways in the cell
Cell Effectors
Often permanent and slow step
The effects of the signal are carried out including
Gene transcription
Chromatin structure
Cytoskeletal change
Cell proliferation (division)
Cell survival
Protein synthesis rate

6. Extracellular Signaling in a Nutshell
The signaling cell produces a particular type of signal molecule that is detected by the target cell. The target cells possess receptor proteins that recognize and respond specifically to the signal molecule.
Responds to that signaling molecule  can result in a lot of different downstream effects.

7. Seem Simple? Think Again
How many different signaling molecules
exist?
HUNDREDS
How do you think this effects
a signals ability to be transduced?
Each cell responds selectively
to a mixture of signals
Disregards some
Reacts to others
What complications can arise?
One signal, binding to one type of receptor protein, can cause a variety of effects in the target cell
Cells have an assortment of different receptors, making them sensitive to many signals
Such effects include altering cells shape, movement, metabolism, and gene expression
** Also keep in mind that the different cells respond to the same signal in different ways
2. Signals can act together and can evoke totally different responses.
**For example, one combination can enable a cell to survive. Another combination may cause cell division.
*** Three major types of receptors - Receptor Tyrosine Kinases, G- Protein Coupled Receptors, Steroid Hormone Receptors

8. Cellular Suicide? What do you think happens in the absence of signals?
In most cases, cells kill themselves.

9. Strengthening and Maintaining a Signal
Recall Synaptic Signaling Pathway
How can we alter/strengthen a signal?
Neuroplasticity – ability to reorganize neural pathways based on new experiences

10. 4 Stages to Neuroplasticity
Induction
Neuron realizes input needs to be changed
Selectivity
Type of change is based on input parameters (gain or loss)
Expression
Synaptic efficiency is changed
Maintenance
Change is maintained over long period of time
Postsynaptic neuron realizes that a particular input needs to be changed
Asks the question: Is this signal important to me?
Partially dependent on time -> quick succession of signals will build on one another and strengthen
Steady, slow input will not
Changes may involve chemical, electrical, or even structural changes
Can occur in a variety of ways -> one we will mention today is recurrent network dynamics
Neuronal communication can be point to point – info passed to different regions
resonant – activity can bounce back and forth between two regions
cyclic – activity can circle within one region or multiple regions
Regardless of the type of neuronal communication used, these occur often lead to the development of short term memory = learning

11. How do you think a memory forms??
Wanna Make a Memory?
What is learning?
The ability to acquire new knowledge/ skills through instruction or experience
What is memory?
Process by which learning is maintained over time
How do you think a memory forms??
CELL SIGNALING!
Can discuss short term memory.
Modifications occur in the brain  change in the internal structure of the neurons, the most notable being in the area of synapses, and an increase in the number of synapses between neurons
Learning tasks cause activity to be maintained
**Newly learned info. is “stored” in short term memory – depends on electrical and chemical signaling in the brain
During brain repair following injury, plastic changes are geared toward maximizing function in spite of damaged brain.
In rats. One area damaged. Surrounding cells underwent changes in function and shape allowing them to take on function of damaged cells. NOT EFFECTIVE IN HUMANS.
Same can be said for other aspects of tissue engineering. New signaling pathways must be created, or existing pathways must be refined at times in order to maintain or fix a problem in the body.