how do molecules form living, moving, reproducing cells? 1683, leeuwenhoek: “an unbelievably great...

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How do Molecules form Living, Moving, Reproducing Cells? Leeuwenhoek: “An unbelievably great company of living animalcules, ming more nimbly than any I had ever seen up to this time. The bigge heir body into curves in going forwards." ncis Crick: “Every living cell and every biological macromolecule i natural selection, which had acted over billions of generations to y from ordinary physics and chemistry”

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Page 1: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

How do Molecules form Living, Moving, Reproducing Cells?

1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly than any I had ever seen up to this time. The biggest sort bent their body into curves in going forwards."

1988, Francis Crick: “Every living cell and every biological macromolecule is the end result of natural selection, which had acted over billions of generations to produce complexity from ordinary physics and chemistry”

Page 2: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Molecular Hierarchy of the Cell

DNA Proteins(Enzymes and Motors)

Protein Assemblies (Cytoskeletal Filaments)

→ →

Page 3: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Moving Parts: Motor Proteins on Polymer Tracks

Page 4: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

The CiliumThe Mitotic Spindle

Cellular Machines based on MTs and motors

Page 5: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

“The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists”.

(Alberts, B (1998) Cell 92: 291).

Protein Machine MotorReplication Machinery Helicase

Transcription Machinery RNA polymerase

Mitochondrial ATP synthase F1F0 ATPase

Bacterial Flagellum Flagellar rotary motor

Muscle Sarcomere Myosin-2

Lamellipodium Dendritic Actin Network

Cilium MT motors

Mitotic Spindle MTs and mitotic motors

Assembly and Function? Biochemistry, Genetics, Microscopy, Quantitative Modeling.

Page 6: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Bacterial (prokaryotic) Cells.

Page 7: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Locomoting Eukaryotic Cells.

Page 8: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Mechanism of Eukaryotic Cell Locomotion.

Page 9: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Scanning E.M. of the leading edge.

Page 10: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

E.M. of Actin Filaments in the Leading Edge.

Page 11: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Ribbon Diagram of Atomic Structure of Actin.

Page 12: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Structure of Actin Filaments – helical symmetry.

Page 13: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Actin Filament Assembly and Force Production.

Page 14: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Actin filament polymerization drives Listeria Motility.

Page 15: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Listeria Motility

Julie TheriotStanford University Medical School

Page 16: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Eukaryotic Cell Reproduction; Mitosis and Cell Division.

Page 17: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Mitosis studied in the Drosophila melanogaster Syncytial Embryo

Sullivan Lab

GFP-tubulin; histone-RFP;480 seconds total time(Ingrid Brust-Mascher)

Page 18: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Mitosis in Drosophila Embryos.

MOTOR PROTEINS AND MICROTUBULE-BASED MACHINES.

Page 19: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Mechanism of Mitosis.

Metaphase

Anaphase A

Anaphase B

Page 20: How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly

Cytokinesis in Animal Cells.