Physics at nano/micro scales

Learning Materials: Key TopicsLearning Materials: Key TopicsBiology dominated by weak interactions Biomolecules undergo self-assembly

AbstractAbstractEngineering students are eager to learn about the prospects of nanotechnology to impact biology, e.g., of having nanorobotsnanorobotsthat can treat cancer, one cell at a time.

To address this need, a Bionanotechnologycourse has been developed at UMD and taught for the past five years (since 2006).

Introduction & MotivationIntroduction & MotivationNew Scientist poll in 2011 on “What technology will have the biggest impact on human life in the next 30 years?” Winner: Nanobots that can fight cancer.

A Course on Bionanotechnology: Introducing Engineers to A Course on Bionanotechnology: Introducing Engineers to Biophysical and Biomimetic PrinciplesBiophysical and Biomimetic Principles

Prof. Srinivasa R. Raghavan, University of MarylandProf. Srinivasa R. Raghavan, University of Maryland

Developmental HistoryDevelopmental History Issues for DiscussionIssues for DiscussionHow much basic biology should engineering students know (regardless of department)? This will dictate how much time gets spent on background material.

What physical principles form the core of bionano-technology? Is there a consensus among various scientists? (e.g., currently there is strong overlap with colloid science.)

Mathematics and biochemistry: At what level should these be used? Currently, the math is limited to algebra and basic calculus, and the chemistry to basic organic/physical.

Larger Issues for DiscussionLarger Issues for Discussion2011 Frontiers of 2011 Frontiers of Engineering Education Engineering Education SymposiumSymposium

Irvine, CaliforniaIrvine, CaliforniaNovember13 November13 -- 1616

The focus is on physical principles and on showing “how biology does nanotechnology”, i.e., what principles are inherent in the design of biological sub-cellular structures.

Future engineers will require a foundation to be able to design bionanostructures. Biology shows that self-replicating nanobots exist!Thus, engineers should be taught the physical principles inherent in biology.

Nanobot!

Ribosome = Nanomachine!

Textbooks / Reading Materials

Learning Materials and OrganizationLearning Materials and OrganizationLectures (Powerpoint) Topics Covered

Course taught to > 150 undergrads (seniors) and > 100 grad students at UMD. Students have come from various Engineering (ChBE, BioE, MechE, MatSE) and Science depts (Phys, Chem, Food Sci)

Course evaluations have generally been very good (avg. score > 3.7/4.0).

0

20

40

60

2006 2007 2008 2009 2010 2011

Number of students

3.03.23.43.63.84.0

2006 2007 2008 2009 2010

Teaching evaluation score

Lecture 3. Proteins: Structure, FoldingLecture 3. Proteins: Structure, Folding

Biopolymers vs. synthetic polymers

Protein size vs. synthetic polymer size

Proteins as function of temperature: Denaturing

Why do proteins fold?

Energy scale and types of interactions

Protein Folding Relies on Weak, Non-Covalent BondsProtein Folding Relies on Weak, Non-Covalent Bonds

A folded protein mainly derives its stability from the large number of weak, non-covalent bonds between different parts of the molecule.

The combined strength of these bonds far exceeds kBT (e.g., 10-20 kBT).

Suppose the following shape is desired for afolded protein

many weakbonds

many weak bonds helpcreate a specific shape

few strongbonds

single strong bondmaintains shape here

but shape is differentin other places

ENCH 468N/648N; BIOE 689N

Lecture 3. Proteins: Structure, FoldingENCH 468N/648N; BIOE 689NENCH 468N/648N; BIOE 689N

Lecture Lecture 3.3. Proteins: Proteins: Structure, FoldingStructure, Folding

Prof. Srinivasa R. RaghavanDepartment of Chemical & Biomolecular Engineering

University of Maryland

Prof. SrinivasaProf. Srinivasa R. RaghavanR. Raghavan

Department of Chemical Department of Chemical & Biomolecular Engineering& Biomolecular Engineering

University of MarylandUniversity of Maryland

Protein Binding to Ligand: MovieProtein Binding to Ligand: Movie

Movie of protein binding to ligand: http://www.youtube.com/watch?v=Ms_ehUVvKKk

1. DNA, RNA and their assembly aided by proteins: DNA condensation, RNAi2. DNA-protein higher-order assembly: Viral capsids: Osmotic ejection of DNA3. Lipid assembly into micelles and bilayers: based on molecular geometry4. Lipid membranes, cell walls: rigidity, cholesterol; stabilizn by PEG5. Protein assembly in membranes: sensing, signal transduction, antibodies6. Drug delivery vehicles: targeting by antibodies, targeted cancer therapy

1. Simplest biomolecular assembly: Protein folding: akin to coil-globule transition 2. Protein folding: Weak interactions: hphobic, H-bond, vdW, electrostatic3. Protein-ligand binding: Co-operativity and its utility, biotin-avidin4. Protein assembly: Filaments and fibrils: Connection to cell motility5. Protein assembly: Gels and networks: Connection to clotting cascade6. Protein assembly (misfolded): Amyloid plaques, Connection to disease

1. Physics at nano/micro scales: Low Reynolds number, Brownian motion2. Biomolecular building blocks: Polymers, amphiphiles

Assembly at the nanoscale only or microscale as well?What about assembly of cells into tissues? Should this course encompass the range of biomimetic structures?

What exactly is the scientific foundationof nanotechnology in general and bionanotechnology in particular?

How can we equip engineers to be able to design biomimeticand bio-inspiredstructures in the future?

Viscous effects dominateover inertial effects

Brownian motion (kBT)is a significant factor

+

Lipids

DNA / RNA

Motor Proteins

Filamentous Proteins

Myosin

+ endF-actin– end

DNA nanobox

Crowding Interactions

Electrostatic Interactions

van der Waals Interactions

Hydrophobic Interactions

B

6k T

RD

Stokes-Einstein equation

protein

ligand