1. Review of Cell Biology ChemEng 575: Tissue Engineering Lecture 2 January 22 nd, 2015

2. Before we can be tissue engineers, we need to understand the biology

3. Animal Cell Structure 3

4. Figure 6-2 Molecular Biology of the Cell (© Garland Science 2008) 4 What is the Central Dogma of Molecular Biology

5. Figure 4-4 Molecular Biology of the Cell (© Garland Science 2008) 5 What holds together the double strands of DNA?

6. Figure 4-5 Molecular Biology of the Cell (© Garland Science 2008) Why does DNA form a double helix? 6

7. What’s the difference between DNA and RNA? 1.RNA is single stranded. 2.RNA can create secondary structures other than a double helix. 3.RNA = Uracil. DNA = thymine. 4.RNA = ribonucleic acid. DNA = deoxyribonucleic acid. 5.RNA is temporary.

8. Figure 17-67 Molecular Biology of the Cell (© Garland Science 2008) All the cells in your body contain the same DNA, but aren’t equal. Why? RNA is temporary mRNA (proteins) made on-demand

9. Figure 3-2 Molecular Biology of the Cell (© Garland Science 2008) PROTEINS. Made from amino acid building blocks 9 R

10. Protein structure Tertiary structure Quaternary Structure: Protein FUNCTION: Electrostatic Interactions 10 Primary Structure Secondary Structure BONUS: What is a post-translational modification?

11. How do cells change what proteins they translate? Transcription Factors Epigenetics

12. Figure 15-1 Molecular Biology of the Cell (© Garland Science 2008) Extracellular signals transduced via signaling proteins – to – transcription factors, finally altering phenotype

13. Figure 15-4b Molecular Biology of the Cell (© Garland Science 2008) Paracrine Signaling

14. Figure 15-4d Molecular Biology of the Cell (© Garland Science 2008) Endocrine signaling

15. Autocrine signaling

16. Juxtacrine Signaling

17. 17 Human cells are Eukaryotes. Eukaryotes keep their cell functions separated

18. Figure 2-21 Molecular Biology of the Cell (© Garland Science 2008) 18 The cell is a “bag of water” What specialized macromolecule keeps compartments separated? Phospholipids

19. Figure 12-7 Molecular Biology of the Cell (© Garland Science 2008) Lipid bilayers allow separation between water and water, and allow transport 19

20. Figure 17-1 Molecular Biology of the Cell (© Garland Science 2008) Cell Division: Overview

21. Division Limitation: Telomeres 1. why is this good for cells in the body? 2. what challenges does this make for tissue engineering? 21

22. How do cells come together to create functional organisms? Cell: the basic unit of all living things. Tissue: group of similar cells and the materials surrounding them. Organ: composed of two or more tissue types that perform one or more common functions. – E.g. bladder, heart, skin Organ system: group of organs that have a common function or set of functions and are therefore viewed as a unit. Humans have 11 major organ systems Organism: any living thing considered as a whole.

23. Tissue Engineering Challenge: Very difficult to get a drug through the skin! Integumentary System skin, hair, nails, and sweat glands Chemical Engineering Analog: Heat Exchanger Humidifier Solar Panels (Vit D)

24. Skeletal System first to be “engineered” Traditional route for skeletal system engineering: Bio-inert materials Purposes: 1.Replace tissue structure and function, not bio-activity 2.do not entice an immune response once implanted into the body. 3.Have incredible mechanical toughness withstand physiological loading 4.Long lasting in the body (won’t degrade over time) Applications: Skeletal tissue prosthesis (hip, knee replacement) 24 What types of materials would be suitable? Non-corroding metals (titanium, stainless steel) Certain Ceramics Polymer Composites

25. Muscular System Produces body movements, maintains posture, and produces body heat. Consists of muscles attached to the skeleton by tendons Not truly engineered yet. Many working on stem cell-to-muscle cell differentiation techniques.

26. Nervous System A major regulatory system that detects sensations and controls movements, physiologic processes, and intellectual functions. Consists of the brain, spinal cord, nerves, and sensory receptors. BrainGate Neural Interface

27. Endocrine System A major regulatory system that influences metabolism, growth, reproduction, and many other functions. Consists of glands, such as the pituitary, that secrete hormones Not truly engineered yet. Typically treated with repeated injections of hormones or daily pills. Can be adapted to a patch or implanted, permanent device? Stem cell differentiation to islet cells Chemical Engineering Analog (Pancreas): Control System (Positive Feedback Loop)

28. Heart Valves, from cadavers or animals Rat heart lungs Cardiovascular and Respiratory Systems

29. Lymphatic System Removes foreign substances from the blood and lymph, combats disease, maintains tissue fluid balance, and absorbs fats from the digestive tract. Consists of the lymphatic vessels, lymph nodes, and other lymphatic organs. Only bioengineer (Chemical Engineer) working on this is Melody Swartz, EPFL. She studies flow patterns to the lymph using principles of fluid dynamics. Chemical Engineering Analog: Filtration Unit (ion exchanger/separator) Tank (collects fluid) Control unit: Positive feedback loop (recruitment of immune cells)

30. Digestive System mouth, esophagus, stomach, intestines, and accessory organs (2) Filtrate (3) Clean blood out (1) Toxin + blood in Synthetic Filter: retains very large compounds (>100,000 g/mol) + Hepatocytes: process bilirubin (reaction) Filter + hepatocytes (4) Back to patient Chemical Engineering Analog: Filtration Unit (liquid phase extraction)

31. Urinary System kidneys, urinary bladder, and ducts that carry urine. Chemical Engineering Analog: Filtration Unit (ion exchanger/separator) Continuous flow (or semi-batch) reactor

32. Cell Types – Quick Breakdown

33. Muscle Cells: 3 Types Contraction, Movement

34. Nerve Cells: Information Relay

35. ____blasts and ____cytes and ____clasts: Sense, Turnover, replace tissue 35 Skin = FIBROblast Cartilage = CHONDROcyte Bone = OSTEOcyte, OSTEOblast, OSTEOclast

36. Epithelial Cell: Barriers, separation

37. Adipocyte: Metabolism

38. Now you’re ready! Find a tissue in need Establish design criteria – what does it do and what are the key functions? Cells (?) + Material

39. Wiki SignUp from Tuesday 1.Get account! 2.First one Thursday! 3.Page due same day, 4p 4.Open slots: extra credit 1/3 letter grade

40. Paper SignUp from Tuesday Sign up sheet is online, too big to show here First one Tuesday! Everyone read the paper! Open slots: extra credit – 1/3 letter grade