Triangulation sensing

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Short description: Mathematical theory

Triangulation sensing is a mathematical theory describing the computational steps to recover the location of a source from the fluxes estimated on small windows located on a test surface. The source emits random particles in a medium. The reconstruction steps of the gradient source from the fluxes of diffusing particles arriving to small absorbing receptors are decomposed in several steps:

  1. Estimating the arrival of Brownian particles to the small windows located on the test surface.
  2. Inverting the Laplace's equation to estimate the position from the fluxes based on a triplet of windows.
  3. Reduce the uncertainty by averaging the noise on several triplets.[1]

This theory provides a framework to study neural navigation in the brain.[2][3]

Computing the diffusion fluxes to small window with respect to the source location

The mathematical formulation consists in considering diffusing cues that have to bind to N narrow windows located on the surface of a three dimensional shaped object, typically a ball (in dimension 3) or a disk in dimension 2. M windows ranging between 10 and 50 are located on a ball B(a) of radius a. Individual cue molecules are described as Brownian particles. The cues are released from a source at position x0 outside the ball. The triangulation sensing method consists in reconstructing the source position from the steady-state fluxes estimated at each narrow window for fast binding, i.e. the probability density function has an absorbing boundary condition at the windows.[4]

Steady-state Laplace's equation

The steady-state gradient P0(x) is obtained by integrating the diffusion equation from 0 to infinity, which is equivalent to resetting the diffusing particles after they disappear through a window. It is given by the solution of the mixed-boundary value problem (where D is the diffusion coefficient)

DΔP0(x)=Qδ(xx0) for x3Ω

P0n(x)=0 for x,Ωr

P0(x)=0 for xΩa.

The probability fluxes associated with P0(x) at each individual window Ωa(ϵj) of size ϵj can be computed from the fluxes and depend on the specific window arrangement and the surface of the domain Ω. The parameter Q>0 can be calibrated so that there are a fixed number of particles located in a given volume. At infinity, the density P0(x) has to tend to zero in three dimensions. More complex domains could be studied if their associated Green's function can be found explicitly.

In dimension 2, although the probability density P0(x) diverges when x, the splitting probability between windows is finite because it is the ratio of the steady-state flux at each window divided by the total flux through all windows:

Jk=ΩkP0(x)ndSxqΩqP0(x)ndSx.

In two-dimensions, due to the recurrent property of the Brownian motion, the probability to hit a window before going to infinity is one, thus the total flux is one:

qΩqP0(x)ndSx=1.

The construction of the solution uses an inner and outer solution describe below.

Boundary layer analysis in dimension 2

The inner solution is constructed near each small window[5] by scaling the arclength s and the distance to the boundary η by η¯=ηϵ and s¯=sϵ, so that the inner problem reduces to the classical two-dimensional Laplace equation[6]

Δw=0 in +2,wn=0 for |s¯|>12,η¯=0,w(s¯,η¯)=0 for |s¯|<12,η¯=0.

The far field behavior for |x| and for each hole i=1, 2 is wi(x)Ai{log|xxi|logϵ}+o(1), where A_i is the flux Ai=2π01/2w(0,s¯)η¯ds¯.

The general solution of equation for n=2 is obtained from the outer solution of the external Neumann-Green's function

ΔxG(x,y)=δ(xy) for x+2

Gnx(x,x0)=0 for x+2.

Given for x,x0+2 by G(x,x0)=12π(ln|xx0|+ln|xx0¯|), where x0¯is the symmetric image of x0through the boundary axis 0z.

Construction of the general solution

The uniform solution is the sum of inner and outer solution (Neuman-Green's function) P(x,x0)=G(x,x0)+A1{log|xx1|logϵ}+A2{log|xx2|logϵ}+C, where A1,A2,C are constants to be determined.

To that purpose, the behavior of the solution near each point xi is crutial. In the boundary layer, we get

P(x,y)Ai{log|xxi|logϵ}.

Using this condition on each window, we obtain the two conditions:

G(x1,x0)+A2{log|x1x2|logϵ}+C=0

G(x2,x0)+A1{log|x2x1|logϵ}+C=0.

Due to the recursion property of the Brownian motion in dimension 2, there are no fluxes at infinity, thus the conservation of flux gives: Ω1P(x,y)ndSx+Ω2P(x,y)ndSx=1. In the limit of two well separated windows (|x1x2|1), using the condition for the flux, we get for each window i=1,2, ΩiP(x,y))ndSx=πAi (the minus sign is due to the outer normal orientation), thus πA1+πA2=1. We finally obtain the system

{G(x1,x0)G(x2,x0){log|x1x2|logϵ}+(A2A1)=0A1+A2=1π.

To conclude, the absorbing probabilities are given by

{P1=πA1=12+π2G(x2,x0)G(x1,x0){log|x1x2|logϵ}=1214ln|x2x0||x2x0¯||x1x0||x1x0¯|{log|x2x1|logϵ}.P2=πA2=12+π2G(x1,x0)G(x2,x0){log|x1x2|logϵ}=1214ln|x1x0||x1x0¯||x2x0||x2x0¯|{log|x1x2|logϵ}.

These probabilities precisely depend on the source position x0 and the relative position of the two windows. When one of the splitting probabilities (either P1 or P2) is known and fixed in [0,1], recovering the position of the source requires inverting the previous equations. For P2=α[0,1], the position x0 lies on the curve

Ssource={x0 such that|x1x0||x1x0¯||x2x0||x2x0¯|=exp((4α2){log|x1x2|logϵ})}.

To conclude knowing the splitting probability between two windows is not enough to recover the exact the source x0 , because it lies on one dimensional curve solution. However the direction can be obtained by simply checking which one of the two probability is the highest.

Inverse problem: computing the source location by triangulation

To reconstruct the location of a source from the measured fluxes, at least three windows are needed. With two windows only, a source located on the line perpendicular to one of the connecting windows would, for example generate the same splitting probability P1=P2, leading to a one dimensional curve degeneracy for the reconstructed source positions x0.

Reconstructing the source location x0 from the splitting probabilities,[7] requires to invert a system equation. Starting from the general solution as given above, we get for three windows:

P(x,x0)=G(x,x0)+A1{log|xx1|logϵ}+A2{log|xx2|logϵ}+A3{log|xx3|logϵ}+C,

where A1,A2,A3,C are constants to be determined. The three absorbing boundary conditions forP(x,x0)leads to the system of equations

G(x1,x0)+A2{log|x1x2|logϵ}+A3{log|x1x3|logϵ}+C=0

G(x2,x0)+A1{log|x2x1|logϵ}+A3{log|x2x3|logϵ}+C=0

G(x3,x0)+A1{log|x1x3|logϵ}+A2{log|x2x3|logϵ}+C=0,

with the normalization condition for the fluxes πA1+πA2+πA3=1. With Δ123=(logd13d12d32ϵ)24logd12ϵlogd13ϵ, and using the notations dij=|xixj|, we obtain the solution

A1=1πA2A3.

A2=logd13d12d32ϵ(G30G10+1πlogd13ϵ)(G10G20+1πlogd12ϵ)logd132ϵ2)Δ123.

A3=logd13d12d32ϵ(G20G10+1πlogd12ϵ)(G10G30+1πlogd13ϵ)logd122ϵ2)Δ123

To conclude, we can specify the flux values α>0 and β>0 such that α+β<1, with α=πA1=Ω1P(x,y))ndSxand β=πA2=Ω2P(x,y))ndSx.

To conclude, when two fluxes are know, the flux coefficients A1,A2,A3can be computed and the position x0 can be reconstructed from the three equations.[8][9]

Generalization to three dimensions

With three windows in a x-y plane in the confirguration x1=(0,0,0),x2=(d,0,0)andx3=(e,f,0) (window 1 is at the origin and window 2 is on the x-axis). Using the leading order from the expansion of the fluxes, the location of the source is the solution of the three non-linear equations

γ12=(x0(1))2+(x0(2))2+(x0(3))2

γ22=(dx0(1))2+(x0(2))2+(x0(3))2

γ32=(ex0(1))2+(fx0(2))2+(x0(3))2,

where γi=2ϵπΦi. Solving for the coordinates of x0 and requiring that x0.x >0, leads to the analytical solution

x0(1)=d2+γ1γ22d

x0(2)=12df[d(e2+f2+γ1γ3)e(d2+γ1γ2)]

x0(3)=12df[(e2+f2)({γ1γ2}2d4)+2de(e2+f2+γ1γ3)(d2+γ1γ2)d2(e4+f4+[γ1γ3]2+2e2[f2+2γ1γ2γ3]2f2[γ2+γ3])]1/2.Thus the position can be recovered from the steady-state fluxes.[8][9][10]

Conclusion

In general, with N windows, no explicit inverse is easily available, hence numerical procedures are used to find the position of the source x0 at any order in ϵ. To find the position of the source x0 from the measured fluxes Φi,i=1...N,we need to invert a system of equations. Each of these equations describe a non-planar surface Si in three dimensions, corresponding to window i and intersecting the half-plane (in the case of the windows located on the half-plane) or the unit ball (in the case of the windows located on the ball). Each pair of surfaces Siand Sj intersect, forming three-dimensional curves Cijand all of these curves intersect at the location of the source x0 . In case of N>3 windows, the system is overdetermined and we can simply choose any combination k, l and m of three fluxes from the N available windows. Any combination lead to the same source position.

References

  1. Dobramysl, U., & Holcman, D. (2018). Reconstructing the gradient source position from steady-state fluxes to small receptors. Scientific reports, 8(1), 1-8.
  2. Kolodkin, A. L.; Tessier-Lavigne, M. (2010-12-01). "Mechanisms and Molecules of Neuronal Wiring: A Primer". Cold Spring Harbor Perspectives in Biology 3 (6): a001727. doi:10.1101/cshperspect.a001727. ISSN 1943-0264. PMID 21123392. PMC 3098670. http://dx.doi.org/10.1101/cshperspect.a001727. 
  3. Blockus, Heike; Chédotal, Alain (August 2014). "The multifaceted roles of Slits and Robos in cortical circuits: from proliferation to axon guidance and neurological diseases". Current Opinion in Neurobiology 27: 82–88. doi:10.1016/j.conb.2014.03.003. ISSN 0959-4388. PMID 24698714. http://dx.doi.org/10.1016/j.conb.2014.03.003. 
  4. Shukron, O., Dobramysl, U., & Holcman, D. (2019). Chemical Reactions for Molecular and Cellular Biology. Chemical Kinetics: Beyond The Textbook, 353.
  5. Pillay, S.; Ward, M. J.; Peirce, A.; Kolokolnikov, T. (January 2010). "An Asymptotic Analysis of the Mean First Passage Time for Narrow Escape Problems: Part I: Two-Dimensional Domains". Multiscale Modeling & Simulation 8 (3): 803–835. doi:10.1137/090752511. ISSN 1540-3459. http://dx.doi.org/10.1137/090752511. 
  6. John., Crank (1956). The mathematics of diffusion. Clarendon. OCLC 1120831223. http://worldcat.org/oclc/1120831223. 
  7. Schuss, Zeev (2009). Theory and applications of stochastic processes : an analytical approach. Springer. ISBN 978-1-4614-2542-7. OCLC 1052813540. http://worldcat.org/oclc/1052813540. 
  8. 8.0 8.1 Dobramysl, U., & Holcman, D. (2019). Triangulation sensing: how cells recover a source from diffusing particles in three dimensions. arXiv preprint arXiv:1911.02907.
  9. 9.0 9.1 Dobramysl, U., & Holcman, D. (2018). Mixed analytical-stochastic simulation method for the recovery of a Brownian gradient source from probability fluxes to small windows. Journal of computational physics, 355, 22-36.
  10. DOBRAMYSL, Ulrich et HOLCMAN, David. Triangulation Sensing to Determine the Gradient Source from Diffusing Particles to Small Cell Receptors. Physical Review Letters, 2020, vol. 125, no 14, p. 148102.