Mathema/cal

Principles of Morphogenesis Applied to Nanoscale Self- Assembly

Bruce J. MacLennan, PhD

Department of Electrical Engineering & Computer Science, University of Tennessee, Knoxville
OBJECTIVES
The Challenge: How can we coordinate the behavior of millions of microscopic agents to assemble complex, hierarchically structured macroscopic systems? Hypothesis: The morphogenetic processes that operate in embryological development can be applied to the selfassembly of complex, hierarchical systems.

EXAMPLE PROBLEM
Assemble a segmented spine with a pair of segmented legs on each spinal segment. Control the number and length of spinal and leg segments. Control the position of the legs.

CAUDAL AND ROSTRAL MORPHOGENS

Caudal Morphogen: Rapidly accumulates in tail tissue Diffuses and degrades Represents proximity to tail tissue - C = DC r2 C D Rostral Morphogen: Accumulates in differentiated segments (S > 0) Diffuses and degrades Represents proximity to differentiated segments - R = DR r2 R D

EXTERIOR SURFACE DETECTION

Inverse quorum sensing: detect when density of neighbors is below a threshold Implemented by morphogen diffusing from segment tissue Modeled by convolution with Gaussian E = [ S < Supb ] kernel determined by diffusion parameters

C/C +

C T (1

C)

DIFFERENTIATION OF IMAGINAL DISKS

Imaginal disk tissue differentiates when: anterior border morphogen in correct range posterior border morphogen in correct range segment density is sufficiently low
-I D = [aupb > a > alwb ^ pupb > p > plwb ^ S (1 S < Supb ] I)

APPROACH
Adopt mathematical descriptions of natural morphogenetic processes to artificial systems Ensure processes will scale up to millions or billions of agents by going to the continuum limit (stochastic PDEs) Nevertheless, maintain complementarity between discrete and continuous models Continuum mechanics of visco-elastic materials (soft matter) Mimic or replace the fundamental morphogenetic processes described by Salazar-Ciudad, Jernvall, and Newman (2003)

CLOCK-AND-WAVEFRONT PROCESS
Vertebrae: humans have 33, chickens 35, mice 65, corn snake 315 characteristic of species How does developing embryo count them? Segments also govern development of organs Clock-and-wavefront model of Cooke & Zeeman (1976), recently confirmed (2008) Depends on clock, excitable medium (cell-to-cell signaling), and diffusion

R/R +

R S (1

R)

SEGMENT DIFFERENTIATION
Tissue differentiates into segment tissue when: segmentation signal () passes through sufficiently far from tail (C < threshold) sufficiently far from previous segments (R < threshold)

FIRST STEPS TOWARD LEG GROWTH

Imaginal disk tissue differentiates to be in T (terminal) state These cell orient outward (i.e., grad S) Begin to move and produce undifferentiated leg tissue (ready for clock-and-wavefront) The figure shows the formation of two segments of the first leg pair Residual morphogens interfere with correct formation of the second pair. More work to be done!

MICROROBOTS, CELLS & MACROMOLECULES

Components are: Both active and passive Simple, local sensors (chemical, etc.) Simple effectors local action (motion, shape, adhesion) signal production (chemical, etc.) Simple regulatory circuits (need not be electrical) Ambient energy and/or fuel Self-reproducing or not

GOAL OF SPINAL MORPHOGENESIS

Controlled sequence of differentiated segments Anterior and posterior regions of segments further differentiated

- S D - S D

+= +=

[ > S S (1

lwb

S)

^ C < Cupb ^ R < Rupb ]

SEGMENT POLARIZATION
+ = [Pupb Cupb > C > Plwb Cupb Posterior Segment Border: ^ > lwb ] Segment tissue differentiates into - P + = P SP (1 P ) P/P posterior border tissue when: D segmentation signal () passes through caudal morphogen (C) concentration is high -P D

CONCLUSIONS
Self-assembly of complex, hierarchically structured systems from microscopic components will require artificial morphogenesis, inspired by embryological development This entails understanding the mathematical structure of morphogenetic processes and applying it in artificial systems Use of a PDE-based notation facilitates scaling to very large numbers of components As an example we have applied the clock-and-wavefront process to simulated assembly of a complex object

GROWTH OF UNDIFFERENTIATED TISSUE

T = density of tissue in terminal (tailbud) state u = direction of motion r = rate of movement or growth M = density of undifferentiated tissue = length of tailbud

A PROGRAMMING LANGUAGE FOR MORPHOGENESIS

Change equations for describing discrete- or continuous-time behavior: - X = F (X, Y ) D Example definition of a diffusible substance:

r -T D -M D

= [G > G ]r0 = = rT / (rT u) = r(u T + T u)

WAVE PROPAGATION
The tissue is an active medium Clock signal causes a patch of tail tissue to fire: emit a pulse of (segmentation morphogen) It diffuses and degrades Sufficiently high stimulates nearby tissue to fire But after tissue fires, it enters a refractory period (determined by a variable ) Ensures unidirectional propagation

Anterior Segment Border: - A + = [Aupb Rupb > R > Alwb Rupb D Segment tissue differentiates into ^ > lwb ] anterior border tissue when: - A + = A SA(1 A) A/A D segmentation signal () passes through rostral morphogen (R) concentration is high

REFERENCES
J. Cooke, E.C. Zeeman (1976). A clock and wavefront model for control of the number of repeated structures during animal morphogenesis, Journal of Theoretical Biology 58: 455476. B.J. MacLennan (2010). Morphogenesis as a model for nano communication, Nano Communication Networks Journal 1: 199208. B.J. MacLennan (2012). Molecular coordination of hierarchical selfassembly, Nano Communication Networks Journal 3: 116128. B.J. MacLennan (2012). Embodied Computation: Applying the physics of computation to artificial morphogenesis, Parallel Processing Letters 22: 124013. I. Salazar-Ciudad, J. Jernvall, S. Newman (2003). Mechanisms of pattern formation in development and evolution, Development 130: 20272037.

substance morphogen: scalar eld vector elds: j order-2 eld behavior: j D = ( T )/2 = j ux change in conc. concentration ux drift vector di usion tensor

LOCATION OF IMAGINAL DISKS

Anterior/Posterior Position: Anterior and posterior border tissues emit anterior (a) and posterior (p) morphogens, which diffuse and degrade Establish opposing gradients by which position can be determined

D + = [G > G ^ K > K ]T D + = + D r2 / - D = /

[ > ^ < ]M

MORE INFORMATION?
a) + Da r2 a p) + Dp r2 p a/a p/p
Email: MacLennan@utk.edu Web: web.eecs.utk.edu/~mclennan [sic]

- a = [A > A ] D - p = [P > P ] D

a S (1 p S (1

RESEARCH POSTER PRESENTATION DESIGN 2012

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