BIO307- Bioengineering principles SPRING 2019

1. BIO307- Bioengineering principles SPRING 2019 Lecture 4 PHYSIOLOGICAL PRINCIPLES Communication Systems in the Body Lecturer: Jasmin Sutkovic 25.3.2019

2. Content • Signaling fundamentals • The nervous system • The Endocrine system • Connections to Biomedical Engineering

3. Introduction • Cells communicate with each other directly or indirectly via molecules called ligands. • In direct cell–cell communication, the ligands are bound to the surface of the cell. • The target cell has specialized proteins called receptors, which are located on the surface, but anchored in the membrane. • Some receptors, such as steroid hormone receptors, are located inside the cell, so the ligand must be able to cross the cell membrane to bind to them.

4. Properties of receptors All receptors have two properties: • 1) they bind specifically to their ligands • 2) they transmit signals inside the cell The binding of ligand to its receptor is similar to the “lock-and-key” fit between an enzyme and its substrate

5. Signal transduction pathway • When signal binds to receptor and ligand attaches to receptor we start a chain reaction of signal transduction to the cell. • Most pathways use enzymes which may act as transducors, converting the signal to another form and they act also as amplifiers, increasing the magnitude of signal.

6. The general mechanism for signal transduction in a cell is: [ligand + receptor] → transducer → amplifier → response. • All functions necessary for growth, differentiation, metabolism, and defense require cells to communicate with other cells. • In fact, many diseases can be traced to a defect in cell communication. • Cancer, for example, can result from either overexpression of oncoproteins, which promote proliferation of cells, or inhibition of tumor suppressor proteins, which normally function to prevent tumor development

8. Many drugs either enhance or inhibit steps in signal transduction pathways

9. Signaling fundamentals

10. Indirect signaling over short distance Paracrinesignaling molecules, such as those used for nerve cell communication, act on target cells in the vicinity of the site of secretion Autocrine signaling molecules act on the cells that secrete them.

12. Cell Surface receptors

15. Secondary messangers Second messengers serve as molecular transducers; they transfer the original signal to another protein that can help carry out the message

16. Phosphorylation and regulation of signal transduction • Phosphorylation (adding phosphate groups) and dephosphorylation (removing phosphate groups) reactions are used frequently in signaling pathways as a way to turn enzymes on and off. • Phosphorylation of proteins is an important modification that the cell uses to help transfer the signal from the receptor to the final effector enzyme.

17. The nervous system • The nervous system functions with the endocrine system to maintain homeostasis • Sense of taste, sight, sound, and smell originate in sensory neurons that send signals directly to the brain. • These sensory organs and their neurons are part of CNS (central nervous system)

18. The endocrine system • Good link: http://www.livescience.com/26496-endocrine-system.html • Collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood, among other things. • Hormones are the chemical messengers of the endocrine system. • In response to a specific demand, an endocrine gland secretes hormones into the blood for distribution throughout the body to stimulate a response in a target organ.

20. Protein hormone signaling • Exp: Insulin and Glucagon hormones • Secreted by pancreas, to control blood glucose levels within a constant range (80–90 mg/dL). • The glucose-sensing beta cells secrete insulin in response to the elevated blood glucose concentration (hyperglycemia). • In contrast, glucagon secretion from the alpha cells is stimulated by a decrease in blood glucose concentration (hypoglycemia). • Thus, insulin is secreted in response to the “fed state” whereas glucagon is secreted in response to the “starved state.”

22. The adaptive immune system • The acquired immune system monitors the internal and external environments for the presence of foreign invaders and implements “attack plans” to eliminate them from the body . • In the normal immune response, only cells that are non-self or foreign are destroyed, whereas self cells are left intact. • Adaptive immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters with that pathogen. • This process of acquired immunity is the basis of vaccination.

23. If the pathogen persists in the body, the “special forces” of the adaptive or acquired immune system are recruited. These forces include Antigen presenting cells (APCs) B cells, and T cells. • The adaptive immune system exhibits two responses: • humoral response • cell-mediated response

25. Connections to biomedical engineering • Why should bioengineers bother with all of this biology, particularly in areas that are not historically important to engineers such as immunology and endocrinology? • The science of cell communication represents one of the important frontier areas for biomedical engineering (BME) and most biomedical engineers are deeply immersed in cellular and molecular biology.

26. Examples • Biomedical engineers are beginning to learn how to build instruments that can interface directly with cells and tissues of the nervous system • Bioengineers can now routinely add or subtract key signaling genes in cells and tissues to improve artificial organ function • Biomedical engineers are making tremendous progress in control and exploitation of immune system function..